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J M Foidart

Publications and source records attributed to J M Foidart.

At least 145 records · Page 8Linked to original sources
PubMed1995

Modulation of the expression of interstitial and type-IV collagenases in coculture of HT1080 fibrosarcoma cells and fibroblasts.

Members of the metalloproteinase family (MMPs) are known to play a crucial role in the metastatic cascade. Here, we report some investigations about the synthesis of interstitial and type-IV collagenases (gelatinases A and B) in a model of coculture of human fibroblasts and HT 1080 fibrosarcoma cells. The interstitial collagenase activity, mainly found in the conditioned medium of fibroblasts, and its mRNA level were increased in the in vitro coculture model. In contrast, gelatinase A was produced by both cell types. The HT 1080 cells additionally synthesised gelatinase B. In coculture, an enhancement of gelatinase A and the presence of its activated form were observed. Northern blot analysis demonstrated that this enzymatic enhancement occurred at a pretranslational level. The stimulation of the interstitial collagenase activity was partially mediated through soluble factor(s), whereas increased gelatinase A appeared to require direct cell-cell interactions. The extracellular matrix component, type-I collagen, stimulated the enzymatic activities released by the individual cells, but it did not modulate the synthesis of interstitial collagenase in coculture. Our results demonstrate that distinct MMPs are modulated by distinct mechanisms, all depending on specific interactions between tumour cells and host fibroblasts.

Blotting, Northern↗
PubMed1994

Epithelial-to-mesenchymal transition in HPV-33-transfected cervical keratinocytes is associated with increased invasiveness and expression of gelatinase A.

The invasive potential of a set of HPV-33- and HPV-33 + ras-transfected cervical keratinocytes was investigated. These cell lines were previously separated into 2 groups according to their behavior on collagen rafts. Cell lines from the first group reconstituted CINIII-like lesions, whereas cell lines from the second group reconstituted epithelia comparable to micro-invasive carcinomas. They were thus postulated to represent distinct stages of cervical carcinogenesis. The present results have shown that lines from group I, which have conserved an epithelial morphology in monolayer, (i) could not invade matrigel when tested in a modified Boyden chamber assay, (ii) produced solely gelatinase B and (iii) were unable to activate exogenous gelatinase A. On the other hand, lines from group II associated epithelial-to-mesenchymal transition (acquisition of elongated morphology, vimentin positivity) with high in vitro invasive potential and with the ability both to produce and to activate gelatinase A. These results strongly support the hypothesis that the epithelial-to-mesenchymal transition and the associated events might be implicated in the progression to the metastatic phenotype.

Blotting, Northern↗
PubMed1994

Differentiation ability and oncogenic potential of HPV-33- and HPV-33 + ras-transfected keratinocytes.

Five HPV-33-immortalized and 5 HPV-33 + ras-transfected cell lines were characterized in terms of growth in soft agar, tumorigenic potential in nude mice, p21 expression, morphology and expression of differentiation markers in organotypic cultures. No striking differences were observed between the HPV-33-immortalized cell lines and their corresponding ras-transfected counterparts as regards their tumorigenicity in nude mice (only one cell line was able to develop tumors in nude mice) or their behavior on lifted collagen gels. However, all the ras-transfected cell lines gave rise to colonies in soft agar while only 2 HPV-33-transfected lines (CK1 and CK4) displayed this property. The 10 cell lines could be divided into 2 groups with respect to their phenotype in monolayer and in organotypic cultures. Lines from group I (CK2, 3, 5 and their ras-transfected homologous lines) shared a typical epithelial phenotype in monolayer and the ability (a) to form an epithelium similar to a CIN-III lesion and (b) to strongly express keratins K1-K10 and involucrin in organotypic cultures. On the other hand, for the lines from group II (CK1, CK4, CK1EJ7 and CK4EJ5), there was a correlation between an elongated phenotype in monolayer and the property (a) to form a structure similar to a microinvasive carcinoma and (b) to express vimentin and keratins K8-K18. These cell lines, exhibiting various transformation-associated alterations, can be considered as an in vitro model representing various stages of HPV-33-associated cervical carcinogenesis.

Animals↗
PubMed1994

Coordinate enhancement of gelatinase A mRNA and activity levels in human fibroblasts in response to breast-adenocarcinoma cells.

Gelatinases/type-IV collagenases are metalloproteinases involved in some carcinoma invasion and metastatic processes. The exact cellular source of the 72-kDa gelatinase A is controversial. We have analyzed the expression of mRNA coding for gelatinase A in vivo by in situ hybridization on breast-cancer tissues. The mRNA for gelatinase A was present in fibroblasts. We have therefore evaluated the gelatinase-A activity in vitro, in co-cultures of different breast adenocarcinoma cell lines and human fibroblasts. In monoculture, none of the tumor cells tested produced detectable amounts of gelatinase A. The gelatinase-A activity was enhanced in cultures of fibroblasts maintained in the presence of MDA-MB 231 or SKBR3 cells, or their conditioned medium. This increased enzymatic activity was evidenced both in the culture medium and in the membrane fraction and was paralleled by enhancement of the steady-state levels of mRNA. These results are an in vitro demonstration of a regulation of fibroblasts gelatinase-A production by soluble factors secreted by breast-tumor cells.

Adenocarcinoma↗
PubMed1994

Role of matrix, fibroblasts and type IV collagenases in tumor progression and invasion.

We have studied the role of the extracellular matrix and host cells in tumor progression and tumor invasion. Our results emphasize the importance of tumoral cell-host cell interactions during this process. Addition of human fibroblasts and/or basement membrane components to human mammary adenocarcinoma cells, when injected into athymic nude mice, results in an increase of take and growth rate of the tumors. Peritumoral extracellular matrix is remodeled through multiple mechanisms: overproduction of matrix components by fibroblasts, enhanced fibroblasts proliferation, modulation of interstitial collagenase production by fibroblasts and retraction of the matrix by tumoral cells. The degradation of basement membranes during the metastatic process is often associated with the secretion of proteolytic enzymes. The 72 kDa type IV collagenase, a metalloproteinase, can be produced by some tumoral cells. However, it appears also to be secreted by peritumoral stromal fibroblasts under the influence of tumoral cells. We have demonstrated the existence of a binding site for this enzyme on the membrane of mammary tumoral cells. These results suggest a cooperation between tumor cells and fibroblasts during basement membrane destruction.

Animals↗
PubMed1994

Expression of gelatinases A and B and their tissue inhibitors by cells of early and term human placenta and gestational endometrium.

BACKGROUND: Human placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. EXPERIMENTAL DESIGN: Several studies have documented the key roles of matrix metalloproteinases and their tissue inhibitors in the invasion of various matrices by cultured trophoblasts. In vitro studies suggest that placentation could result from a balance between the secretion of these enzymes by trophoblast cells and their inhibition by the natural tissue inhibitors (TIMPs) produced by maternal decidual cells. The precise localization and levels of expression of these proteins that account for and control invasion during human placentation in vivo however, have not been described. We have evaluated, in vivo, by immunohistochemistry, Northern blot analysis and in situ hybridization, the expression of two metalloproteinases (gelatinases A and B) and their two tissue inhibitors (TIMPs 1 and 2) in placental villi and placental beds of first and third trimesters of normal pregnancy. RESULTS: Human first trimester intermediate trophoblast produced both gelatinases A and B; these two gelatinases were respectively less and no more detected at term in these cells. We found that both TIMP1 and 2 were also expressed in maternal decidual cells with a dramatic increase of TIMP1 at the term of pregnancy. In floating villi, gelatinase A and TIMP1 were localized in the stromal compartment, whereas gelatinase B and TIMP2 were codistributed in trophoblast cells. CONCLUSIONS: The gelatinases A and B and their tissue inhibitors are thus expressed by specific cells in early and late placental beds and villi. This pattern of expression varies during pregnancy. Therefore, our morphologic study supports biologic findings suggesting that these proteins may participate in placentation.

Blotting, Northern↗
PubMed1994

[Breast cancer invasion: the key role of normal cells of host tissues].

Tumor progression is influenced by extracellular matrices and by soluble factors or cytokines locally produced by host tissue cells (fibroblasts, immune cells ...). Such factors may also accumulate in close association with some extracellular matrix molecules in the tumor. They may also be unmasked during breaking down of extracellular matrices. The most insidious aspect of tumors is their propensity to locally invade normal tissues of the host and to form secondary foci in organs at distant sites from the primary tumor called metastases. During this process, invasive cells come into contact with host tissue cells such as fibroblasts, endothelial cells, macrophages, lymphocytes. These cells are not the passive witnesses of the metastatic cascade but actively participate to the malignant invasion. Through soluble messages (cytokines) and through insoluble molecules of the extracellular matrix, neoplastic and normal cells mutually modulate their activities. Cancer cells regulate the biosynthetic activities of fibroblasts and alter in this way the scaffold of the tumor. Reciprocally, host cells secrete extracellular matrix proteins and cytokines which influence the growth and activities of tumor cells. They also produce at the periphery of tumor cells proteolytic enzymes which promote host tissue destruction and cancerous cells migration. Among these enzymes, matrix metalloproteinases appear to play a key role during invasion and metastasis. Tumors represent thus a complex ecosystem. Tumor cells interact with several components of the extracellular matrix and with host cells (immune cells, fibroblasts, endothelial cells). Such multiple cell-cell and cell-matrix interactions condition angiogenesis, tumor growth, destruction of host tissues, local migration of cancer cells and their metastatic dissemination. It is probable that a precise knowledge of the genes which are selectively activated in tumors under the influence of the host cells or of the tumor cells will allow to define new therapeutic strategies. These treatments will aim not at destroying the metastatic neoplastic cells but at preventing their growth by interfering with their microenvironment.

Animals↗
PubMed1993

Immortalization of human cervical keratinocytes by human papillomavirus type 33.

Ten immortalized cell lines were established by transfection of human cervical keratinocytes (CK) with HPV-33 DNA and some of their characteristics were investigated. The following observations were made: (a) several cell lines have reached over 100 population doublings in vitro; (b) 3 transcripts were observed, 2 being encoded by the E6/E7 open reading frames (ORFs); (c) cytogenetic analyses showed important genetic modifications such as aneuploidy and isochromosome formation of the q arm of chromosome 8; (d) 2 of the 10 cell lines developed colonies in soft agar but none was able to form tumors when injected s.c. into nude mice; (e) Southern analysis suggested that a single copy of HPV-33 is integrated at a single common site within the genome of the 10 cell lines. These immortalized cell lines should be useful for studying mechanisms involved in proliferation, differentiation and neoplastic transformation of CK by HPV-33.

Animals↗
PubMed1993

Microinjection of antifibronectin antibodies in the chicken blastoderm: inhibition of mesoblast cell migration but not of cell ingression at the primitive streak.

The involvement of fibronectin in adhesion and migration of individual mesoblast cells during chicken gastrulation was examined after microinjection of functional and nonfunctional antifibronectin antibodies in the blastoderm during the period of rapid migration of mesoblast cells. The injection of affinity-purified polyclonal antihuman fibronectin antibody (total IgG or Fab fragment) or of monoclonal antichicken cellular fibronectin caused a thickening of the primitive streak, which was composed of loosely connected cells. This effect was most evident at the level of Hensen's node, and very few mesoblast cells were observed migrating in the space between upper layer and deep layer. The obvious explanation of this effect was that the de-epithelialization of upper layer cells persisted in the presence of antibodies, but ingressed cells failed to emigrate from the primitive streak. Immunostaining of microinjected antibodies showed binding to the basement membrane, to the cell surface of mesoblast cells that had migrated before microinjection occurred, and to the cell surface of deep layer cells. Cells that ingressed and detached in the course of reincubation of the embryo possessed little immunolabelling along their cell surface. The results suggest that the failure of ingressed cells to emigrate from the primitive streak and to form mesoblast was due (1) to alterations in adhesion between newly ingressed primitive streak cells, which had the ability to detach but possessed relatively little fibronectin along their cell surfaces and a small number of cell protrusions, and (2) probably to a lack of adhesion of detached cells to the basement membrane, which was blocked by the presence of antifibronectin antibodies. We conclude that the presence of fibronectin in the basement membrane is required for emigration of ingressed cells and migration of mesoblast cells to occur. Once migration has commenced, fibronectin is also deposited along the cell surface of migrating cells, a factor that may increase their mutual adhesion.

Animals↗
PubMed1993

Ultrastructural demonstration of type IV collagen deposits in periductal elastosis in breast cancer.

In a previous study we demonstrated at light microscopical level the presence of variable amounts of type IV collagen in the areas of periductal and interstitial elastosis in breast cancer. The present work was directed towards a further study by immunoelectron microscopy of the distribution of type IV collagen in the areas of periductal elastosis. The semithin sections showed a distinct immunoreactivity of all basement membranes for type IV collagen but no staining of the interstitial stroma. Corresponding ultrathin sections demonstrated a broad basement membrane with immunoreactivity for type IV collagen at its outer side. Many punctiform deposits of type IV collagen were observed in the areas of periductal elastosis but not around normal ducts or vessels. Recently the role of type IV collagen as a structural component on anchoring plaques between the basement membrane and the underlying stroma in the dermis has been emphasized. The results of this study demonstrate the presence of type IV collagen deposits below a thickened basement membrane in breast cancer.

Breast Neoplasms↗
PubMed1993

Enhancement of tumorigenicity of human breast adenocarcinoma cells in nude mice by matrigel and fibroblasts.

The failure of MCF7 cells to induce the formation of tumours after sub-cutaneous inoculation into athymic nude mice can be obviated by the simultaneous injection of an extract of basement membrane proteins (matrigel). Tumour growth is promoted and the latency period is low (2 to 4 weeks). In the absence of matrigel, the simultaneous inoculation of fibroblasts and MCF7 cells also resulted in the development of tumours, but with a longer latency period (about 2 months). The tumorigenic synergy between matrigel and fibroblasts was evidenced by co-inoculating MCF7 cells MDA-MB 231 cells with fibroblasts and matrigel. This co-inoculation decreased the delay of appearance of the tumours and/or accelerated the tumour growth, depending upon the number of fibroblasts injected. Repeated injections of fibroblasts conditioned medium, at the site of inoculum of tumour cells also enhanced tumour growth, suggesting the involvement of soluble factors secreted by fibroblasts. Histologically, tumours induced by co-inoculation of tumour cells and fibroblasts contained more stromal structures including vimentin-positive cells, fibronectin and interstitial collagens. These data suggest that human tumours may be reconstituted and grown in athymic nude mice using basement membrane components and fibroblasts as inductors.

Adenocarcinoma↗
PubMed1993

Reevaluation by image analysis of the effects of fibroblasts, fibronectin or laminin upon colony formation in mouse lungs by B16 melanoma cells.

A recently described personal method based on image analysis of histological sections was used in order to quantify lung colony formation by B16 melanoma cells injected intravenously into the mouse. These tumor cells were preincubated in vitro either with fibronectin (FN), laminin (LN) or fibroblasts (FB), which are implicated in the process of invasion and metastasis. Thanks to this method, a more accurate analysis of lung colonies (section area and number) formed by tumor cells was realized. By image analysis, we show that when FB were mixed with B16 cells, a drastic increase of tumor sections number and area was induced. LN increased the tumor sections area, but not their number. No effect of FN on B16 cells was observed. LN and FN promoted tumor anchorage in the depth of the lungs while FB reduced the latter. These facts could explain the contradictory results obtained by simply counting macroscopically superficial lung colonies. When cultured in vitro, these B16 melanoma cells did not produce any type of IV collagenase, either alone or in the presence of LN or FN, but in cocultures (B16 with 3T3) and in fibroblasts cultures, this enzyme was present. This could explain, among other factors, why the rate of invasiveness exerted by B16 cells is higher when the latter are coinjected with FB.

3T3 Cells↗
PubMed1993

Different mechanisms of extracellular matrix remodeling by fibroblasts in response to human mammary neoplastic cells.

Human breast tumors are often associated with a fibrotic reaction termed desmoplasia. Tumor cells may indirectly modulate the composition of the extracellular matrix by influencing fibroblast properties. They may also directly interact with collagen fibrils leading to retraction of the matrix. We have studied in vitro the influence of various human mammary tumor cells on the proliferation rate of normal human fibroblasts and on their level of collagen synthesis, as well as their release of collagenase activity. Interactions between neoplastic cells and collagen matrix were investigated by incorporation of tumor cells in collagen gels (lattices) and measurement of their retraction. All cells tested (HBL100, SW613, SA52, MDA-MB-231, MCF7, MCF7/6, MCF7 ras, BT20 and T47D) were able to modulate the composition of the extracellular matrix by one or several of the mechanisms investigated. Our results also demonstrate an opposite regulation of collagen and collagenase production. The effects on the collagen metabolism and on fibroblast proliferation are probably mediated by soluble cytokines since they are reproduced by incubating the fibroblasts in the presence of medium conditioned by tumor cells. The desmoplastic reaction may thus result from different mechanisms dependent upon tumor cell types.

Breast Neoplasms↗
PubMed1993

Extensive deposition of basement membrane by tumours: a prognostic factor? A reappraisal.

A loss of the continuous linear deposit of basement membrane around invasive carcinomas has been suggested to correlate with their increased invasiveness. In contrast, extensive basement membrane deposition would represent a more favourable prognosis. The Engelbreth-Holm-Swarm (EHS) tumour, a transplantable neoplasm, is widely used for its ability to synthesize and deposit large amounts of basement membrane components. We have evaluated the metastatic potential of this neoplasm 2 months after subcutaneous inoculation. Histological examination of lung sections revealed the presence of numerous metastatic foci. The metastatic cells retained their organization into clusters surrounded by extracellular matrix. Both the 72 kDa and the 92 kDa type IV collagenases were detected by zymography in Triton or urea extract (matrigel) of primary tumour. These results cast doubt on the hypothesis that the extensiveness of basement membrane deposition might always be of prognostic value by being inversely correlated with the degree of invasiveness of a carcinoma.

Animals↗
PubMed1993

[Physiology of the pregnant woman and risk factors].

Physiological adaptations of the pregnant woman involve the circulatory, respiratory, digestive, renal, endocrine and metabolic systems. Their precise knowledge allows the clinician to verify the quality of the adaptation of the pregnant woman and to avoid unnecessary treatment of physiological changes misconsidered as pathological changes in reference to prepregnancy standards.

Adaptation, Physiological↗
PubMed1993

Interactions between tumoral MCF7 cells and fibroblasts on matrigel and purified laminin.

A reconstituted basement membrane (matrigel) and/or fibroblasts promote the growth of human breast tumors in athymic nude mice. We have investigated in vitro the effect of matrigel or purified glycoproteins (laminin and fibronectin) on tumoral MCF7 cells-fibroblasts interactions. In coculture on matrigel, MCF7 cells organized into clusters attached on top of fibroblasts aggregates. During the process resulting in tumor cells-fibroblasts aggregation, fibroblasts actively migrated while MCF7 cells were passively transported. Using purified proteins, specific antibodies and synthetic peptides, we show that cell aggregation induced by immobilized and soluble laminin is antagonized by exogenous fibronectin or fibronectin synthesized by fibroblasts.

Amino Acid Sequence↗
PubMed1992

Tumor cell surface-associated binding site for the M(r) 72,000 type IV collagenase.

We have studied the capacity of two human breast adenocarcinoma cells, MDA-MB231 and MCF-7, to bind exogenous M(r) 72,000 type IV collagenase by both morphological and radioreceptor binding assays. By indirect immunofluorescence, staining with a specific anti-M(r) 72,000 type IV collagenase antibody was strongly induced when cells were preincubated with the purified enzyme. Scatchard plot analysis indicated the existence of a binding site for the M(r) 72,000 type IV collagenase with high affinity for both cell lines (Kd = 2 x 10(-9) M). These results are the first demonstration of the existence of a tumor cell membrane-associated putative receptor for a member of the matrix metalloproteinase family, as previously evidenced for the urokinase-type plasminogen activator.

Adenocarcinoma↗