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PubMed1996

Blast colony forming cell-binding capacity of bone marrow stroma from myelodysplastic patients.

A specific stroma function can be quantitatively assessed by counting the stroma-adherent blast cell colonies (CFU-BL) that are formed from normal plastic nonadherent mononuclear bone marrow cells (PNAMNC) after a short-term coincubation ("panning") with the preformed stromal layer. In order to obtain information of stroma function in myelodysplasia (MDS), the "CFU-BL-binding capacity" of stroma from normal bone marrow and from patients with MDS were compared. Stromal cell cultures were established from mononuclear bone marrow cells in microplate cultures cultured with or without 10(-6) M hydrocortisone. CFU-BL-binding capacity was studied by counting blast colonies seven days after panning, and the results were expressed as CFU-BL/10(3) PNAMNC. Normal marrow stromal layers bound CFU-BL only if they were cultured with hydrocortisone, while MDS stromal layers also bound CFU-BL in the absence of hydrocortisone. For further studies of the function of MDS stroma, the effect of growth factors (stem cell factor [SCF], G-CSF, interleukin 3 [IL-3] and their combinations) on CFU-BL binding by normal or MDS stroma has also been compared. Twenty-hour incubation of the stromal layers with a standard dose (100 ng/ml) of various hemopoietic growth factors (IL-3 alone or in combination with SCF, G-CSF alone or in combination with SCF) did not have any effect on CFU-BL binding by normal marrow stroma, but increased the CFU-BL binding by stromal layers from MDS bone marrow. These findings suggest that although stromal microenvironment in MDS is capable of supporting hemopoiesis, bone marrow stroma from MDS patients differs in some characteristics from the normal stroma.

Anti-Inflammatory Agents↗
PubMed1999

Origin of stroma cells in long-term bone marrow cultures from patients with acute myeloid leukemia.

Bone marrow stroma cells from patients with acute myeloid leukemia (AML) display a variety of functional abnormalities. In order to determine whether this is related to an imbalance in the proportion of different stroma cell types or to integration of leukemic progeny into the regulatory cell network, stroma layers were established in mycophenolic acid-treated long-term marrow cultures from 16 patients with AML and 42 controls and analyzed by means of simultaneous membrane immunofluorescence and interphase cytogenetics. Macrophages were identified by CD14 expression, fibroblasts by staining with the AS02 antibody, and malignant cells by leukemia-specific numerical chromosome aberrations, including monosomy 7 and trisomy 8. Compared with normal controls, there was a slight decrease in the proportion of stroma fibroblasts (52+/-27% versus 77+/-5%) in 10-week-old cultures from patients with AML. Two of five AML patients with trisomy 8 and both patients with monosomy 7 had evidence of leukemic stroma cells. Most malignant cells were CD14+ macrophages (3.8-98.1% of all CD14+ cells), but some were AS02+ (2.8-5.2%). AML stroma layers showed a reduced capacity to support the growth of normal hematopoietic cells in standard two-stage long-term cultures, but this was unrelated to the presence or absence of leukemic stroma elements. In conclusion, AML populations vary with respect to their ability to produce a malignant microenvironment. Functional defects in the hematopoietic microenvironment, however, are not limited to AML patients with cytogenetically abnormal stroma cells, but extend to cases without evidence of malignant stroma cells.

Acute Disease↗
PubMed1989

Does chondroitin sulfate have a role to play in the morphogenesis of the chick primary corneal stroma?

This paper makes three points about how the chick corneal epithelium lays down the primary stroma, an orthogonally arranged array of well-spaced, 20-nm-diameter collagen fibrils. (1) Isolated corneal epithelia will, when cultured, lay down de novo stromas whose fibril-diameter distribution, fibril spacing, and proteoglycan profile are similar to those laid down in vivo. They differ from embryonic stromas in two ways: first, much of the chondroitin sulfate is released to the medium and, second, there is a relatively small amount of orthogonal organization. Epithelia seem only to lay down such stromas if they are separated from their original stromas with dispase, which leaves an intact basal lamina, and spread out, basal lamina downward, on a Nuclepore filter (poresize, 0.1 micron). (2) Chondroitin sulfate (CS), the predominant proteoglycan (greater than 85%), seems to play no significant role in collagen fibrillogenesis in vitro. Stromas laid down in its absence were indistinguishable from controls as assayed by fibril diameter, organization, and spacing and the amount of collagen synthesized. For these experiments, epithelia were cultured in the presence of hyaluronidase, which degrades CS, and p-nitrophenyl beta-D-xyloside, which inhibits the formation of links between the core protein and glycosaminoglycan side chains in the PG; the absence of intact CS was confirmed by gel filtration. We suggest that, in vivo, CS may facilitate the interfibrillar movement that takes place as the cornea grows. We have also found that keratinase, which degrades the very small amount of keratan sulfate present in the primary stroma, has no effect on stromal deposition. (3) There are substantial amounts of unidentified matrix components in primary stromas laid down both in vivo and in vitro. This conclusion was drawn from SEM observations on both types of stroma after they had been freeze-dried, a process which does not condense hydrated macromolecules. Even after being treated with hyaluronidase to remove the CS, substantial amounts of interfibrillar matrix were still present. Until these components are identified and their interactions with collagen are understood, the mechanisms responsible for stromal morphogenesis are unlikely to be understood.

Animals↗
PubMed2003

Neuroepithelial interactions in prostate cancer are enhanced in the presence ofprostatic stroma.

OBJECTIVES: To develop an in vitro model that tests the involvement of prostatic stroma in the active reciprocal interactions between malignant epithelial cells and nerves that occur in perineural invasion. METHODS: Each of three metastatic prostate cancer cell lines (LnCaP, PC3, and DU-145 at 10(3)) was co-cultured in sextuplet experiments with a human prostate stromal cell line (HTS-40C at 10(3)) and a mouse dorsal root ganglion in matrigel for 13 days. Carcinoma/ganglia co-cultures (10(6) cells) in the absence of stroma served as controls. Areas of carcinoma cell growth (day 1), neurite growth (days 1 and 3), and perineural invasion (neuroepithelial halo area, day 11) were quantified. RESULTS: Mean neurite outgrowth was enhanced in the presence of stroma with LnCaP and PC3, but not with DU-145. Perineural invasion and carcinoma cell growth were enhanced in the presence of stroma in experiments with all three cell lines. The mean cell area (in square millimeters) increased 54.7% with LnCaP in the presence of stroma (P <0.001). PC3 and DU-145 growth was enhanced 88.5% and 43.4%, respectively, in the presence of stroma. The mean neurite growth (in millimeters) on days 1 and 3 increased 50.8% and 70.8% with LnCaP in the presence of stroma. This enhancement was observed with PC3 by 88.1% and 64.5%. The mean neurite growth decreased in the presence of stroma with DU-145 by 4.9% and 5.4%. Perineural invasion increased 33.8% in the presence of stroma with LnCaP and 24.3% and 26.1% with PC3 and DU-145, respectively. CONCLUSIONS: These novel findings strongly suggest active stromal participation in perineural invasion. The identification of specific stromal factors may suggest ways of preventing the progression of prostate cancer.

Animals↗
PubMed1994

Morphometric quantitation of stroma in human benign prostatic hyperplasia.

OBJECTIVES: Human benign prostatic hyperplasia (BPH) consists of three major histologic components: stroma, epithelium, and luminal space. For the relief of bladder outlet obstruction caused by BPH, quantitation of the histologic composition of BPH may aid in selecting treatment. To investigate variation between patients in the stromal percentage of BPH, we performed quantitative morphometry on specimens from patients with clinically significant bladder outlet obstruction obtained by three procedures: open prostatectomy, transurethral resection of the prostate (TURP), and prostate needle biopsy (PNB) just prior to TURP. METHODS: Ten specimens obtained by each surgical procedure were analyzed. Specimens were stained with antibody to muscle-specific actin to mark the stroma; quantitation of stroma was accomplished by computer image analysis. RESULTS: The percentage of stroma in all BPH cases ranged from 49.9% to 76.7% (mean, 65.4%, SD = 7.4). No significant difference was observed when comparing samples obtained by the three procedures (p = 0.70). Smooth muscle stromal composition was also quantified in PNB specimens. For these samples, a significant inverse relationship was found between the percentage stroma in the biopsy and the percentage of stroma composed of smooth muscle (r2 = 0.49; p = 0.021). CONCLUSIONS: The data demonstrated that the largest component of BPH was stroma, which comprised approximately 50% to 75% of the total hyperplastic tissue. The mean and range of stromal percentage were similar whether investigating large tissue samples from open prostatectomies or small samples from needle biopsies. PNB data indicated that an increased percentage of stroma may be due to increased nonmuscular elements in the stroma.

Antibodies, Monoclonal↗
PubMed2000

The capacity of connective tissue stromas to sustain myelopoiesis depends both upon the growth factors and the local intercellular environment.

In adults, haemopoiesis is located in the bone marrow, where it is tightly regulated by cytokines and by a physical association of haemopoietic progenitors with the stroma. However, in pathological situations, haemopoiesis can be partly or fully dislodged to peripheral tissues. It is not clear which are the requirements for a given peripheral stroma to sustain haemopoiesis. Using the growth factor-dependent cell line FDC-P1, we have compared the myelopoietic capacities of a murine bone marrow-derived cell line S17, a liver inflammatory granuloma-derived stroma (GR) that sustains haemopoiesis, and normal skin fibroblasts (SF) that sustain neither survival nor proliferation of myeloid cells. All three stromas expressed mRNA for major haemopoietins with the exception of IL-3. Despite the incapacity of SF to sustain FDC-P1 cells, the biologically active GM-CSF could be recovered from all the studied stromas by treatment with high-salt buffers that release non-covalently bound molecules from stroma cells. Glycosaminoglycans purified from stromas had distinct effect on the GM-CSF-mediated proliferation of FDC-P1 cells: those purified from S17 and GR cells were stimulatory, whereas those obtained from SF cells were slightly stimulatory at low concentration, but inhibitory at the higher ones. We conclude that the quality of the stroma pericellular glycoconjugates is determinant for the ability of a given stroma to sustain myelopoiesis, even when biologically active haemopoietins are locally produced.

Animals↗
PubMed2003

Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas.

In the exocrine organs, breast and pancreas, colloid carcinoma (CC, pure mucinous carcinoma), characterized by well-circumscribed lakes of mucin that contain scanty, detached malignant cells, has a significantly better prognosis than conventional ductal carcinomas (DCs). It has been speculated by us and others that an inverse polarization of cells may be responsible for the accumulation of extracellular mucin. Another possibility is that this mucin is biochemically and biologically distinct from the mucin secreted by the conventional carcinomas of these organs. This study was undertaken to investigate these two hypotheses: 1) To test whether there is indeed an alteration in cell polarity in CC. Immunohistochemical stains for luminal surface glycoproteins (carcinoembryonic antigen in pancreas and MUC1 in breast) were performed in 18 pancreatic and 30 mammary CCs and compared with the expression pattern in DCs (37 pancreatic and 47 mammary) and normal ducts. The results disclosed that these glycoproteins were expressed predominantly in the stroma-facing surfaces of CC cells, in contrast to the DCs, in which the expression was either on the luminal surface (in well-differentiated areas) or dispersed throughout the cell, intracytoplasmic in the poorly differentiated areas. Ultrastructural examination performed on 10 breast and two pancreatic CCs showed the condensation of mucigen granules (generally underlying an apical-type cell membrane) in the stroma-facing surface in all cases. In contrast, in the DCs (five pancreatic and five mammary), no clustering of mucigen granules was identified in the cytoplasm facing the stroma in any of the cases. Furthermore, no external lamina or basement membrane was detected in any of the CCs, whereas in the DCs, a distinct (in 3 of 10) or discontinuous (4 of 10) external lamina separated the tumor cells from the stroma. 2) To determine the expression frequency of MUC2 in CCs and to compare it with that in DCs and normal tissue, immunohistochemical stains with MUC2 (clone ccp58) were performed. MUC2 expression was detected in 18 of 18 pancreatic and 30 of 30 breast CCs and was exceedingly rare in DCs (1 of 136 pancreatic DC and 3 of 47 mammary, p <0.0001 in both organs). No labeling was detected in normal ducts. In conclusion, it appears that coupling of two factors is important for the distinctive morphologic characteristics and slow growth of CCs: The first one is the alteration in cell orientation as evidenced by the direction of surface glycoproteins and secretory organelles to the stroma-facing surface of the cells and the disruption of cell-stroma interaction as manifested by lack of basal lamina formation. Apparently, this altered polarity allows the CC cells to secrete the mucin toward the stroma. The mucin produced, MUC2 (also called gel-forming mucin), is highly specific for CC and is known to form strong bonds with the stroma, and also was found recently to have tumor suppressor activity. This distinctive mucin, accumulated in the stroma surrounding the CC cells, may act as a containing factor, slackening the spread of the cells.

Adenocarcinoma, Mucinous↗
PubMed2001

Prolactin receptor expression in the epithelia and stroma of the rat mammary gland.

The importance of prolactin (PRL) in regulating growth and differentiation of the mammary gland is well known. However, it is not well established whether PRL acts solely on the mammary epithelia or if it can also directly affect the mammary stroma. To determine where PRL could exert its effects within the mammary gland, we investigated the levels of expression and the localization of the PRL receptor (PRLR) in the epithelia and stroma of the rat mammary gland at different physiological stages. For these studies, we isolated parenchymal-free 'cleared' fat pads and intact mammary glands from virgin, 18-day-pregnant and 6-day-lactating rats. In addition, intact mammary tissues were enzymatically digested to obtain epithelial cells, free of stroma. The mammary tissues, intact gland, stroma and isolated epithelia, were then used for immunocytochemistry, protein extraction and isolation of total RNA. PRLR protein was detected in tissues using specific polyclonal antisera (PRLR-l) by immunocytochemistry and Western blot analysis. Messenger RNA for PRLR was measured by ribonuclease protection assay. Immunocytochemistry and Western blots with the PRLR-1 antisera detected PRLR in wild-type rat and mouse tissues, whereas the receptor protein was absent in tissues from PRLR gene-deficient mice. PRLR was found to be present both in the epithelia and stroma of mammary glands from virgin, pregnant and lactating rats, as determined by immunocytochemistry and Western blotting. Western blots revealed the predominance of three bands migrating at 88, 90 and 92 kDa in each of the rat mammary samples. These represent the long form of the PRLR. During pregnancy and lactation, PRLR protein increased in the epithelial compartment of the mammary gland but did not change within the stromal compartment at any physiological stage examined. We also found PRLR mRNA in both the epithelia and stroma of the mammary gland. Again, the stroma contained lower levels of PRLR mRNA compared with the epithelia at all physiological stages examined. Also, the PRLR mRNA levels within the stroma did not change significantly during pregnancy or lactation, whereas PRLR mRNA within the epithelia increased twofold during pregnancy and fourfold during lactation when compared with virgin rats. We conclude from this study that PRLR is expressed both in the stromal and epithelial compartment of the mammary gland. This finding suggests PRL may have a direct affect on the mammary stroma and by that route affect mammary gland development.

Animals↗
PubMed1981

Non-uniform swelling properties of the corneal stroma.

The swelling properties of the anterior and posterior stroma of bovine and rabbit corneas were examined by three different methods. The results show that the posterior stroma can swell more than the anterior stroma. Also, at a given swelling pressure, the posterior stroma is more hydrated than the anterior stroma. In a third experiment it is demonstrated that the posterior stroma is also more hydrated in the living eye. It is concluded that the stroma is not a homogeneous structure. The superficial stroma has different physiological properties from the deep stroma. These differences must be taken into account in theoretical models of corneal deturgescence.

Animals↗
PubMed1990

Effects of homologous and heterologous stroma-free hemoglobin and polyhemoglobin on complement activation, leucocytes and platelets.

This is a study of the effects of stroma-free hemoglobin(Hb) and polyhemoglobin on C3 and C3a levels and on blood cell counts. The effects of membrane stroma from red cells and endotoxins on complement activation were also investigated. Plasma samples from rats were incubated with hemoglobin solutions or control solutions. C3 was measured using anti-rat C3 by nephelometric method. C3a was measured using radioimmunoassay. C3 and C3a were also determined in rats receiving hemoglobin solutions, red cell stroma solutions, or a solution containing complement activators (membrane stroma and bacterial endotoxins). There were no significant differences in C3 or C3a levels between the plasma incubated with hemoglobin solutions and the control plasma incubated with saline (P greater than 0.05). Compared with the saline incubated plasma, C3 was significantly lower and C3a significantly higher in the zymosan treated plasma (P less than 0.01). In hemoglobin infused rats, there was no significant difference between pre-versus post-infusion values in C3 and C3a. There was a significant increase in C3a in the rats receiving stroma suspension (P less than 0.05) or stroma and endotoxins (P less than 0.02). Polyhemoglobin and stroma-free hemoglobin did not cause significant changes in total leucocyte, differential, or platelet counts. Our study suggests that purified stroma-free Hb and polyHb do not activate complement, and that C3a is a more sensitive parameter for monitoring complement activation than C3. On the other hand, contaminates in hemoglobin preparations, such as membrane stroma or endotoxins, activate the complement system.

Animals↗
PubMed1984

Effect of red blood cell stroma on the reticuloendothelial system clearance and killing of Streptococcus pneumoniae.

Previous studies from this laboratory have shown that thermal injury can cause sufficient intravascular hemolysis to depress reticuloendothelial system (RES) phagocytic function and that the injection of red blood cell (RBC) stroma depresses RES function and increases susceptibility to experimental shock. The present study evaluated the effect of thermal injury and RBC stroma on susceptibility to infection with Streptococcus pneumoniae as well as the effect of RBC stroma on the RES clearance and killing of the bacteria. The mortality rate following pneumococcal infection was increased after thermal injury from 0% to 100% (P less than .01), and with the injection of RBC stroma (0.5 ml/100 g) mortality increased from 20% to 80% (P less than .01). Hepatic uptake of heat-killed S. pneumoniae was depressed from 64% to 44% of the injected dose following the injection of RBC stroma. RBC stroma depressed complement CH50 levels by 31%. The reduction in the number of viable S. pneumoniae present in the liver between 30 min and 4 hr following bacterial challenge was decreased in animals receiving RBC stroma. This was interpreted as an indication of impaired hepatic bactericidal function and was associated with an increase in the number of circulating viable S. pneumoniae. It is concluded that the increased susceptibility to pneumococcal infection induced by RBC stroma was probably due to an impairment in hepatic clearance and killing of the bacteria. The depressed bacterial clearance could have been contributed to by the stroma-induced decrease in complement levels. This study further supports the hypothesis that the intravascular hemolysis caused by thermal injury contributes to the increased susceptibility to infection following this form of injury.

Animals↗
PubMed2003

The corneal stroma is endowed with a significant number of resident dendritic cells.

PURPOSE: Dendritic cells (DCs) comprise a system of highly efficient antigen-presenting cells (APCs) that initiate immune responses. The purpose of this study was to examine the normal stroma for the presence of DCs and other bone marrow (BM)-derived cells. METHODS: Normal uninflamed corneas of BALB/c and other murine strains were excised, and immunofluorescence single- and double-staining for multiple markers was performed for examination by confocal microscopy. Corneal buttons were placed in culture and immunocytochemistry and flow cytometry performed. RESULTS: MHC class II(+)CD80(+)CD86(+) cells were found in the periphery of the anterior normal stroma. These cells were CD45(+), CD11c(+)CD11b(+) suggesting a BM-derived and monocytic DC lineage. In a surprising finding, significant numbers of MHC class II(-)CD80(-)CD86(-) cells were found in the center of the anterior stroma. These cells were also CD45(+)CD11c(+)CD11b(+) but CD3(-), GR-1(-), keratan sulfate(-), and CD8alpha(-), reflecting an immature precursor phenotype of myeloid DC. In addition to DC subsets in the anterior stroma, a CD11c(-)CD11b(+) population of BM-derived cells was found primarily in the posterior stroma, representing monocytes/macrophages. These cells were rarely present in the anterior third of the normal stroma. Further, CD14(+) precursor-type DCs were found throughout the stroma. These in vivo findings were not strain specific and were confirmed by immunocytochemistry and flow cytometry analyses of cells derived from corneal explants and by transmission electron microscopy. CONCLUSIONS: This study demonstrates that, in addition to the known Langerhans cells in the corneal epithelium, at least three BM-derived cell subsets reside in the normal corneal stroma.

Animals↗
PubMed1998

Interaction of prostate epithelial cells from benign and malignant tumor tissue with bone-marrow stroma.

BACKGROUND: Metastases of prostate cancer form selectively within the skeleton. To understand this metastatic spread, we studied the ability of prostate epithelial cells to grow and proliferate within the bone marrow, using primary coculture. METHODS: Prostate epithelia and fibroblasts were prepared from men with benign prostatic hyperplasia (n = 13) and cancer of the prostate (n = 10). Confluent cultures of bone-marrow stroma or fibroblast controls were prepared in 96-well plates, and identical plates were treated with detergent to expose the extracellular matrix of the cells. Epithelial cells were seeded onto either cells or matrix, and their growth characteristics were determined by counting increases in colony size and number over time. Further experiments evaluated the effects on epithelial growth when cells were exposed to media conditioned by these stroma, using an MTT assay. RESULTS: Results showed that for epithelial cells derived from malignant (or benign) tissue, the median value of the total area of colonies formed on bone-marrow stroma was 2.1 (benign, 2.6) mm2, in contrast to 0.3 (benign, 0.4) mm2 or 0.25 (benign, 0) mm2 when these cells were cocultured with fibroblasts from benign or malignant prostates, respectively. Statistics indicated that growth was significantly greater on bone-marrow stroma than on control stroma (P < 0.005). However, no significant stimulation of epithelial cell growth was seen when these epithelial cells were cultured on extracellular matrix from bone-marrow stroma or when exposed to bone-marrow stroma-conditioned media in comparison to fibroblast controls. No statistical differences were found between the formation of colonies from malignant tissue in comparison to benign. CONCLUSIONS: This system allows the investigation of bone-marrow stroma colonization by primary prostate epithelial cells, and could be developed for the study of metastasis.

Bone Marrow Cells↗
PubMed1989

The epigenetic influences of bone marrow and fetal liver stroma cells on the developmental potential of Ly-1+ pro-B lymphocyte clones.

The Ly-1+ Mac-1+ B-220+ CC11+ progenitor clones LyD9 and LyB9 were previously shown to give rise to Ly-1+IgM+ B lymphocytes either in vivo or in vitro by co-culture with nonlymphoid accessory cells from spleen and lipopolysaccharide. The clones did not generate T lymphocytes either in vivo or in vitro. We now find that both LyD9 and LyB9 progenitors are induced to differentiate in vitro by co-culture with the RP.0.10 bone marrow stroma clone or with heterogeneous marrow-adherent stroma cell populations obtained from adult mice into Ly-1-IgM+ B lymphocytes as well as myeloid GM1.2+ Mac-1+ cells. We could obtain evidence that a high proportion of LyD9 and LyB9 cells already switched off expression of Ly-1 and CC11 (interleukin 3 receptor) surface molecules 2 days after initiation of the cultures, and by days 8-10 of culture no detectable Ly-1+ cells and only about 20% CC11+ cells were observed. Ly-1 surface expression could not be re-induced on the progeny of LyD9 and LyB9 progenitors generated under the influence of marrow stroma cells. Remarkably, the LyD9 and LyB9 progenitors gave rise to both Ly-1+IgM+ and Ly-1-IgM+ B cells upon culture with heterogeneous stroma monolayers obtained from 18-day fetal liver. Finally, the differentiating property of the stroma cells for the LyD9 and LyB9 progenitors could not be replaced with soluble factors produced either spontaneously or after stimulation by the marrow stroma cells. Our results show the importance of epigenetic influences provided by a given microenvironment on the developmental potential of B cell progenitors. They provide direct evidence that the same pro-B lymphocyte can give rise to both Ly-1+ and Ly-1-IgM+ B cells depending on both the time of development and the tissue of origin of stroma cells with which the B cell progenitor interacts. Also, the results strongly suggest that cell contact between the stroma cell and the B cell progenitor is essential to induce rearrangement and expression of the Ig genes in pro-B lymphocytes.

Animals↗
PubMed1996

Interstitial stroma and carcinogenesis: ultrastructural observations in the rat bladder treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

This study describes ultrastructural alterations of the interstitial stroma in the rat bladder epithelium during N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-induced bladder carcinogenesis using scanning (SEM) and transmission (TEM) electron microscopy with NaOH treatment. The results obtained with SEM demonstrated the occurrence and development of stroma protrusions which exhibited pipe-like structures in the rat bladder epithelium following administration of BBN. Number and size of blood vessel sections also gradually increased both in the stroma and within the layer of the proliferated epithelial cells as examined by light microscopy (LM) and TEM. In this study stroma alterations were not only observed in malignant lesions of rat bladder, but hyperplastic lesions were also accompanied by stroma alterations. It is suggested that: (1) the interstitial stroma of the rat bladder epithelium may exhibit pathological changes in structure and these changes may correlate with the progression of epithelial cell proliferation following administration of BBN and (2) one of the most important alterations in the stroma is the occurrence of neovascularization, which may induce structural modification of the stroma in the processes of bladder tumor growth and development.

Animals↗
PubMed1988

Acquisition of type IX collagen by the developing avian primary corneal stroma and vitreous.

Previous investigations from our laboratory and others have demonstrated that type II collagen, once thought to be a cartilage-specific molecule, is also a component of both the primary corneal stroma and the vitreous of embryonic chickens. In the present immunohistochemical study we have examined the expression in these embryonic matrices of another "cartilage-specific" collagen, type IX, along with type II. In the cornea, type IX collagen is in the primary stroma, but is not detectable in the mature, secondary stroma. Even within the primary stroma this collagen has a brief, transitory existence. It first appears in the peripheral stroma at the time the endothelial cells begin to migrate along its posterior surface, and spreads throughout the stroma during the following 24-36 hr. The epitopes on type IX collagen then suddenly become undetectable just before this matrix swells and becomes populated by the periocular mesenchymal cells (future keratocytes). In comparison, collagen type II (along with type I) is present in the stroma before and long after these events. Deposition of immunodetectable type IX collagen in the developing corneal stroma thus seems to be independent of type II. In the vitreous, we observed type IX collagen along with type II as soon as authentic vitreous could be identified and at all subsequent stages of development. In this tissue, therefore, the expression of collagen types IX and II appears to be coordinate.

Animals↗
PubMed1987

5 alpha-androstane-3 beta,17 beta-diol hydroxylating enzymes in stroma and epithelium of human benign prostatic hyperplasia (BPH).

As enzymatic hydroxylation of 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) may be a factor in controlling the 5 alpha-dihydrotestosterone (DHT) content in the prostate, we were interested in activity and distribution of these enzymes in epithelium and stroma of human benign prostatic hyperplasia (BPH). The enzyme activities were measured after mechanical separation of BPH tissue from 15 patients of various ages into stroma and epithelium, and optimization of the in vitro transformation of 3 beta-diol to hydroxylated products, which were analyzed by HPLC. The main results were: (1) 3 beta-diol was hydroxylated at C-7 alpha, C-7 beta, C-6 alpha, and C-6 beta. (2) The mean Michaelis constant Km (nM +/- SEM) for hydroxylation at C-7 alpha(beta) (168 +/- 21) was significantly lower than at C-6 alpha(beta) (601 +/- 43) without differences between stroma and epithelium. (3) Hydroxylation at alpha position dominated significantly over that at beta. (4) The mean maximal metabolic rate Vmax (pmol . mg protein-1 . h-1) of hydroxylation at C-6 alpha was about 7-fold lower in stroma (3.4 +/- 0.2) than in epithelium (23.8 +/- 4.1), concerning the other hydroxylations, Vmax was about 1.6-fold lower in stroma. (5) With increasing age of the patients there was a significant decrease of the 3 beta-diol hydroxylation in stroma and epithelium. It is discussed that the significantly lower activity of 3 beta-diol hydroxylation in stroma compared to epithelium and the decrease of activity with increasing age might potentiate the DHT accumulation in stroma of BPH.

Aged↗
PubMed1989

Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition.

Tumor stroma formation results from the interaction of tumor cells and their products with the host and certain of its normal defense mechanisms, particularly the clotting and fibrinolytic systems. It is a process in which tumor cells render local venules and veins hyperpermeable with the result that fibrinogen and other proteins extravasate and clot, forming an extravascular crosslinked fibrin gel. Coagulation is mediated by an interaction between extravasated plasma clotting factors and tumor-associated and perhaps other tissue procoagulants. Parallel activation of the fibrinolytic system leads to substantial fibrin turnover, but fibrin nonetheless accumulates in amounts, variable from tumor to tumor, that are sufficient to provide a provisional stroma. This provisional stroma imposes on tumor cells a structure that persists even as tumor cells multiply and as the fibrin provisional stroma is replaced by mature connective tissue. The provisional fibrin stroma also serves to regulate the influx of macrophages, and perhaps other inflammatory cells, but at the same time, and in ways that are not fully understood, facilitates the inward migration of new blood vessels and fibroblasts, integral components of mature tumor stroma. Ascites tumors differ from solid tumors in that fibrin gel is not ordinarily deposited in body cavities and, as a result, there is no provisional stroma to impose an initial structure. Tumor stroma generation resembles the process of wound healing in many respects. However, it differs in the mechanism of its initiation, and in the apparent lack of a role for platelets. It also differs fundamentally in that invading tumor cells continually render new vessels hyperpermeable to plasma, thus perpetuating the cycle of extravascular fibrin deposition. In this sense, tumors behave as wounds that do not heal. Largely neglected in this review has been discussion of the numerous cytokines, mitogens, and growth factors that are widely believed to play important roles in tumor angiogenesis and wound healing; i.e., PDGF, FGF, EGF, TGF alpha, TGF beta, TNF, interferons, etc. This omission has been intentional, and for two reasons. First, these cytokines have already received considerable attention [100,123-128]. Second, it is not yet clear how closely the actions of these molecules, as described in vitro, relate to their functions in vivo. At present we are deluged with a surfeit of factors that have the capacity to induce new blood vessel formation in angiogenesis assays; these factors include not only peptides but lipids and even ions [126,129-131].(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Coagulation↗