A rare case of primary lymphoma of the breast and metachronous breast primitive lobular carcinoma: case report.
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Adult↗
Biomedical subjects
A Poggi
Publications and source records attributed to A Poggi.
IL2 triggers a tumor progression process in a melanoma cell line MELP derived from a patient whose metastasis increased in size during IL2/INFalpha biotherapy.
Human melanomas may express both in vivo and in vitro functional IL-Rs and may be expected to directly respond to injected IL2. This may generate biological situations which may be favourable for the patient, but also for tumor progression. Here, we analyse the latter hypothesis. MELP is a melanoma cell line derived from a patient whose metastasis increased in size during IL2/IFN alpha biotherapy [correction of biotheraphy]. These cells have been characterized in vitro for their phenotype and for their sensitivity to IL2. In vitro MELP cells express an IL2-R alpha(+) beta(+) gamma(-) phenotype and IL2 treatment induces the acquisition of new functional characteristics represented (i) by the increased surface expression of two markers of metastatic evolution (ICAM-1 and CD44); (ii) by the stable induction of the IL2-R gamma with the appearance of functional IL2-R beta complex, which are also recognized by GM-CSF; (iii) by the inhibition of transcription of a regulatory cytokine such as IL6; (iv) by a differential effect of IL6 on CD44 surface expression in MELP cells treated or not with IL2 (MILG cells); (v) by the acquisition of faster growth rates and appearance of piling up and multilayer cellular organization; (vi) by the development of rapidly growing tumors in nude mice. IL2 induces in MELP cells a tumor progression process that could mimic the metastatic evolution observed in vivo during biotherapy. Therefore, MELP phenotype may help to define a subset of patients in which IL2 therapy may trigger unfavourable evolution.
Adult↗
The human leukocyte antigen (HLA)-C-specific "activatory" or "inhibitory" natural killer cell receptors display highly homologous extracellular domains but differ in their transmembrane and intracytoplasmic portions.
Natural killer cells express clonally distributed receptors specific for major histocompatibility complex class I molecules. The human leukocyte antigen (HLA)-C-specific receptors have been molecularly identified and cloned. They exist not only as inhibitory (p58) but also as activatory (p50) receptors. Here we show that p50 and p58 are highly homologous in their extracellular regions formed by two Ig-like domains. In contrast, major differences exist in their transmembrane and cytoplasmic portions. Whereas p 58 displays a 76-84-amino acid cytoplasmic tail containing an unusual antigen receptor activation motif, p50 is characterized by a shorter 39-amino acid tail. In addition, whereas p58 has a nonpolar transmembrane portion, p50 contains the charged amino acid Lys. These data strongly suggest that receptors with identical HLA-C allele specificity can mediate functions of opposite sign owing to their different transmembrane/cytoplasmic portions.
Amino Acid Sequence↗
CD31-triggered rearrangement of the actin cytoskeleton in human natural killer cells.
In this report, we analyze whether CD31, also known as platelet-endothelial cell adhesion molecule-1 (PECAM-1), can transduce an outside-in signal in human natural killer (NK) lymphocytes in vitro. We show that CD31, but not HLA class-I cross-linking triggers an outside-in transmembrane signal in NK lymphocytes, mediating cell spreading and cytoskeletal rearrangement. These phenomena are Mg2+, but not Ca2+ dependent, suggesting that signal transduction elicited by CD31 cross-linking may involve an associated integrin. Two possible candidates would be alpha v and alpha L, whose function is known to depend on Mg2+. However, the CD31-induced cytoskeletal rearrangement was not reduced by the use of alpha v- or alpha L-specific F(ab')2, suggesting that CD31 could transduce a signal by itself or by association with a still-undefined integrin. Moreover, talin, but not vinculin or tubulin, appears to co-localize with actin microfilaments in the membrane ruffles of NK cells that undergo cytoskeleton rearrangement following CD31 cross-linking. Both spreading and cytoskeletal rearrangement appear to be regulated by intracellular cyclic-3',5'-adenosine monophosphate (cAMP). Indeed, the activator of the adenylyl cyclase, forskolin, inhibited cell spreading and cytoskeletal rearrangement induced by CD31 cross-linking. This phenomenon was also observed using the membrane-permeants cAMP analog Sp adenosine-3', 5' -cyclic monophosphothioate (Sp-cAMPS), but not its inactive isomer Rp-cAMPS. Likewise, adhesion of NK lymphocytes to NIH/3T3 murine fibroblasts transfected with the cDNA encoding human CD31 was blocked by increasing intracellular cAMPS levels. We suggest that intracellular cAMP may be involved in CD31-mediated signal transduction, and may regulate NK-endothelial cell adhesion and possibly, the tissue localization of NK cells.
3T3 Cells↗
Dissection of lymphocyte function-associated antigen 1-dependent adhesion and signal transduction in human natural killer cells shown by the use of cholera or pertussis toxin.
The effect of the guanosine triphosphate-binding protein (G-protein) inhibitors cholera toxin (Ctx) and pertussis toxin (Ptx) has been analyzed on lymphocyte function-associated antigen 1 (LFA-1)-dependent adhesion and signal transduction in human natural killer (NK) cells. Ctx, but not Ptx, inhibited the LFA-1-dependent adhesion of NK cells to tumor target cells which constitutively express the intercellular cell adhesion molecule-1 (ICAM-1) and to NIH/3T3 mouse fibroblasts stably transfected with human ICAM-1. This effect was detectable only by the use of the entire Ctx but not of the Ctx B subunit. In addition, Ctx could inhibit both NK cell binding and spreading to purified ICAM-1 protein. NK cell treatment with Ctx modified neither the surface expression of LFA-1 nor its Mg2+ binding site. These findings, together with the absence of any detectable effect of Ctx on the constitutive phosphorylation of LFA-1 alpha, suggests that this toxin modifies the avidity of LFA-1 for ICAM-1 by acting on LFA-1-cytoskeletal protein association. Unlike Ctx, Ptx did not affect NK cell adhesion. The effects of Ctx and Ptx are unlikely to depend on intracellular levels of cyclic adenosine 3',5'-monophosphate (cAMP), since a strong increase of cAMP was induced by both toxins. Moreover, this was confirmed by the observation that the LFA-1-dependent adhesion was not inhibited by the adenylate cyclase activator forskolin (FSK), the phosphodiesterase inhibitor isobutyl-1-methylxanthine (IBMX), or both, which increase intracellular cAMP levels. Unlike the differential effect on cell adhesion, both the intracellular calcium [Ca2+]i increase and phosphoinositide breakdown mediated via LFA-1 were consistently inhibited in a dose-dependent manner by both Ctx and Ptx. Also in this case, the inhibitory effect did not depend on an increase of intracellular cAMP as indicated by NK cell treatment with FSK, IBMX, or both. Further evidence of the involvement of G-proteins in LFA-1-mediated signal transduction was the inhibitory effect of the GDP analog guanosine-5'-O-2-thiodiphosphate (GDP beta S) on LFA-1-mediated calcium mobilization. Taken together, our data provide evidence that the LFA-1-mediated NK cell adhesion and signal transduction are partially independent phenomena which may be regulated by different G-proteins.
Adenylate Cyclase Toxin↗
Expression of human NKRP1A by CD34+ immature thymocytes: NKRP1A-mediated regulation of proliferation and cytolytic activity.
In this study, we show that NKRP1A is expressed and functions on a subset of immature human thymocytes. We took advantage of the monoclonal antibody (mAb) 191B8 that was obtained by immunizing mice with cultured human thymocytes characterized by an immature surface phenotype [CD2- CD3- CD4- CD8- stem cell factor receptor (SCFR)+] and expressing cytoplasmic CD3 epsilon chain. The 191B8 antibody homogeneously reacted with the immunizing population but not with most unfractionated thymocytes. It stained a minor population of resting immature thymocytes co-expressing CD34, SCFR, or both. Following culture of the CD34+ or CD34- fractions of CD2- CD3- CD4- CD8- purified immature thymocytes with recombinant interleukin-2 (rIL-2), the 191B8-defined antigen was expressed on virtually all cells even when 191B8+ cells were removed from the starting population. On the other hand, no 191B8+ cells were detected in fresh or cultured thymocytes expressing a more mature phenotype. Biochemical analysis of 191B8 mAb-reactive molecules revealed, under non-reducing conditions, two bands displaying apparent molecular masses of 80 and 44 kDa and a single band of 44 kDa under reducing conditions. Digestion with proteases indicated that the 80-kDa form represented a homodimeric form of two 44-kDa molecules, while deglycosylation with N-glycanase suggested the existence of four N-glycosylation sites. Transfection of COS7 or NIH3T3 cells with hNKRP1A cDNA showed that the 191B8 mAb recognized NKRP1A as shown by both immunofluorescence analysis and immunoprecipitation experiments. Functional studies showed that the 191B8/NKRP1A molecule mediated strong inhibition of the cytolytic activity of cultured CD2- CD3- immature thymocytes against a panel of tumor target cells. More importantly, 191B8 mAb induced proliferation of CD2- CD3- fresh thymocytes which was not increased by rIL-2. Thus, we propose that NKRP1A molecules, which are expressed in highly immature thymocytes, may play a regulatory role in their growth and function.
Antigens, CD34↗
Physical and functional association of CD45 and CD3-TCR complex on CD1+ human thymocytes. Evidence that the engagement of CD45 molecules can prevent CD1+ thymocytes from apoptosis.
In this study the effects of CD45 engagement on CD3-TCR-driven stimulation of CD1+ human immature thymocytes have been analyzed. Simultaneous cross-linking of CD45 and CD3 antigens on highly purified CD1+ thymocytes reduced the number of cells undergoing apoptosis after 16 h of in vitro culture. This cell population might represent immature thymocytes committed in vivo to die by programmed cell death (PCD). CD45 engagement could also increase the number of cycling CD1+ thymocytes; of note, the large majority (> 95%) of dividing cells expressed the CD1 molecule at the cell surface, indicating that proliferating cells were actually represented by immature thymocytes. These data suggest that the CD45 molecule might play a role in the rescue of immature thymocytes from PCD during differentiation. Along this line, we found that activation of CD1+ thymocytes via the CD3-TCR complex could be enhanced by CD45, both in terms of transcription and surface expression of IL-2R. These effects might be explained by the finding that the CD45 molecule (but not its isoforms CD45RO and RA) was physically associated with the CD3-TCR complex at the cell surface of CD1+ human thymocytes, as shown by co-precipitation and co-capping experiments. Finally, cross-linking of CD45 and CD3 antigens led to the expansion of CD3+ thymocytes co-expressing CD4 and CD8, indicating that simultaneous engagement of CD45 and CD3 molecules can block CD1+ cells at the double-positive (CD3+CD4+CD8+) differentiation stage. On the other hand, stimulation through CD3 resulted in the expansion of thymocytes showing a mature phenotype (CD3+CD4+ or CD3+CD8+). Altogether, these findings suggest that the CD45 molecule is involved both in early activation and in the regulation of CD1+ thymocyte differentiation.
Antibodies, Monoclonal↗
Effect of superantigens on human thymocytes: selective proliferation of V beta 2+ cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulation.
The effects of toxic shock syndrome toxin-1 (TSST-1) on human thymocytes and their CD4/CD8-defined subsets have been analyzed. Postnatal thymocyte cell suspensions were cultured with 5 ng/ml TSST-1 for different time intervals. A strong cell proliferation of CD3+/TCR+ cells, characterized by selective expansion of cells expressing TCR V beta 2, occurred. In these cultured thymocytes, V beta 2+ cells were detected in all subsets including CD4-CD8+ cells. CD4-CD8+ thymocyte populations (obtained by depletion of CD4+ cells) were further analyzed for their ability to directly respond to TSST-1. An efficient cell proliferation occurred; however, it was completely abrogated upon removal of HLA class II+ cells (representing 10% of fresh thymocytes depleted of CD4+ cells). The HLA class II dependency of TSST-1 mediated functions was further documented at the clonal level. Thus, in the presence of TSST-1, CD4-CD8+ V beta 2+ clones efficiently lysed the HLA class II+ Raji target cells but not the corresponding HLA class II- variant RJ 2.2.5. Analysis of the effect of TSST-1-induced secondary stimulation on cultured (V beta 2+-enriched) thymocytes resulted in a selective depletion of V beta 2+ cells due to apoptotic cell death.
Bacterial Toxins↗
Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasia.
Cysteinyl leukotrienes (i.e. LTC4, LTD4), produced by activated leukocytes or by transcellular metabolism may act at different levels on vascular smooth muscle cells (VSMC) during inflammatory process or atherosclerosis. We studied the effect of LTC4, LTD4, and LTE4 on the in vitro proliferation of rat VSMC, measured by [3H]-thymidine incorporation and cell count. LTD4 had a stronger stimulatory effect on [3H]-thymidine incorporation than LTC4, whereas LTE4 was inactive. The effect of LTD4 on [3H]-thymidine incorporation was dose-dependent, with the maximal activity at 10(-6) M. The stimulatory activity of LTD4 was inhibited in a dose-dependent manner by MK-571, a specific LTD4 receptor antagonist. In addition, MK-571 (1 mg/kg/day) given for at least 1 day after injury in a model of balloon catheter injury of rat carotid artery, provided effective inhibition of myointimal VSMC proliferation, with a 58% reduction of 5-bromo-2'-deoxyuridine (BrdU) uptake in the neointima and 69% reduction of neointimal thickening. Our data support the importance of inflammatory mechanisms in the pathogenesis of atherosclerosis and suggest a possible role for cysteinyl leukotrienes, specifically LTD4, in the control of VSMC proliferation.
Animals↗
Human gamma delta T lymphocytes use N-CAM to interact with the subendothelial matrix.
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Cell Adhesion Molecules, Neuronal↗
p40, a novel surface molecule involved in the regulation of the non-major histocompatibility complex-restricted cytolytic activity in humans.
Four monoclonal antibodies (mAb) termed NKTA255, NKTA72, 1F1 and 1B1 were selected on the basis of their ability to inhibit the cytolytic activity of natural killer (NK) cell clones against P815 target cells. These mAb selectively reacted with normal or tumor cells of hematopoietic origin and displayed a cellular distribution similar to that of CD45 or CD11a/CD18 antigens. Immunoprecipitation experiments showed that they reacted with molecules with an apparent molecular mass of 40 kDa under both reducing and nonreducing conditions ("p40" molecules), thus differing from CD45 or CD11a/CD18 antigens as well as from the "inhibitory" receptors for HLA class I molecules (i.e. p58, CD94 and NKB1 molecules). Double-immunofluorescence analysis of peripheral blood mononuclear cells allowed the identification of three distinct populations on the basis of the fluorescence intensity of cells stained with anti-p40 mAb. p40bright cells were homogeneously HLA-DR-positive, p40medium cells were HLA-DR-negative but co-expressed CD56 antigens, while p40dull cells were all CD3+. Anti-p40 mAb strongly inhibited the lysis of K562 target cells, mediated by fresh NK cells, as well as the lysis of P815 target cells by NK or T cell clones. In addition, in redirected killing assays, anti-p40 mAb strongly reduced the anti-CD16 mAb-induced cytolytic activity of NK cell clones. On the contrary, they did not inhibit either the anti-CD3 or anti-T cell receptor mAb-mediated cytolytic activity of T cell clones or the lysis of allogeneic phytohemagglutinin blasts mediated by specific cytolytic T cell clones. The p40-induced inhibition of the NK cytotoxicity required optimal cross-linking, as anti-p40 mAb could inhibit the lysis of Fc gamma receptor (Fc gamma R)-positive but not of Fc gamma R-negative target cells. In addition, (Fab')2 fragments of anti-p40 mAb failed to inhibit the lysis of Fc gamma R-positive target cells. In conclusion, p40 molecules represent a new type of inhibitory surface molecule that appears to play a general regulatory role in the NK-mediated cytolysis.
Antibodies, Monoclonal↗
Development of human NK cells from the immature cell precursors.
Recent studies provided evidence that functional NK lymphocytes can be derived in vitro from immature cell precursors present in embryonic liver or postnatal thymus. In addition, by applying appropriate culture conditions a lymphoid cell population sharing NK and T-cell properties could be obtained from immature thymic cell precursors. Moreover, the molecular analysis of TCR/CD3 genes revealed that this cell population could represent a frozen stage of the T-cell lymphoid maturation. Altogether, these findings support the concept that a common precursor exists for T and NK cell lineages. In addition the availability of culture conditions which mimic the in-vivo microenvironment required for NK cell maturation may be important to investigate the role of self HLA in the selection of NK lymphocytes equipped with surface receptors specific for autologous HLA-class I alleles.
Animals↗
An instrument for real-time spectral estimation of heart rate variability signals.
A Digital Signal Processor (DSP)-based instrument is proposed for estimating and displaying the Heart Rate Variability (HRV) spectrum in real-time. It consists of an intelligent module which is properly interfaced to an IBM PC and whose operations are independent from the computer's other tasks. In this way, the simultaneous recording of the ECG sequence, needed for the more complete off-line analysis, can be performed by the same host. The employed hybrid spectral estimator (in which a classical FFT analysis follows the autoregressive extrapolation of data) appears to be the most apt for the present fixed point arithmetics implementation. The reliability of the instrument and its accuracy are checked both with suitable test signals and by comparison with the results obtained through off-line analysis of the same ECG tracks. The instrument is presently used for cardiovascular investigations, in particular for quickly picking patients with cardiac autonomic neuropathy (CAN) out of a population of diabetic subjects.
Adult↗
Cytolytic T lymphocytes displaying natural killer (NK)-like activity: expression of NK-related functional receptors for HLA class I molecules (p58 and CD94) and inhibitory effect on the TCR-mediated target cell lysis or lymphokine production.
Natural killer (NK) cells express surface receptors for defined groups of HLA class I alleles. The specific interaction between these receptors and HLA class I molecules expressed on target cells results in inhibition of NK-mediated target cell lysis. In this report, we analyzed whether similar mechanisms were operating in cytolytic T lymphocytes (CTLs) capable of lysing NK-sensitive target cells. T cell clones were screened for their ability to lyse K562 target cells. The selected clones expressed either gamma delta or alpha beta TCR. The majority of these clones failed to lyse the HLA class I+ R8/15375 cell line; however, upon addition of the previously described A6-136 (IgM) or 6A4 F(ab')2 anti-HLA class I mAbs, target cells were efficiently lysed. Lysis of autologous phytohemagglutinin blasts in the presence of anti-HLA class I mAbs occurred primarily with TCR gamma delta+ CTLs. Recognition of HLA class I molecules on target cells implies the expression of NK-related specific receptors in CTL clones. Indeed, phenotypic analysis of > 300 CTL clones with NK-like activity revealed that 28% expressed p58 molecules (specific for HLA-C alleles) while 30% expressed CD94 molecules (specific for the Bw6 specificity). These receptor molecules were found to function as inhibitory receptors, as revealed by the effect of anti-p58 or anti-CD94 mAbs (of IgG isotype) on the lysis of the Fc gamma R+ K562 target cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD↗
Arterial lesions in hypercholesterolaemic Yoshida rats: morphological evaluation.
The aortic wall structure of genetically determined hypercholesterolaemic (Yoshida) and control (Brown-Norway) rats was investigated by transmission and scanning electron and light microscopy. Leucocyte adherence mostly at branch sites and irregular protrusive structures were observed on the endothelial surface of the thoracic aorta of Yoshida, but not of Brown-Norway rats. The subendothelial space of the aortic wall of Yoshida rats was characterized by intimal cushions consisting of smooth muscle cells of 'synthetic phenotype' associated with adhering leucocytes and lipid droplets. Lipid infiltration of the cytoplasm of medial smooth muscle cells was observed on the inner part of the aortic arch and on the lateral parts of the large branches of Yoshida rats. This model of spontaneously hyperlipidaemic Yoshida rats is an appropriate 'moderate' injury system, which may be useful for studies of multiple risk factors for atherogenesis.
Animals↗
The LFA-1/ICAM cell adhesion pathway is involved in tumor-cell lysis mediated by bispecific monoclonal-antibody-targeted T lymphocytes.
We investigated the role of the LFA-1/ICAM, VLA-4/VCAM-1 and CD2/LFA-3 adhesion pathways in the cytolysis of tumor cells mediated by an anti-EGF-R/anti-CD3 bispecific monoclonal antibody (biMAb). The biMAb induced efficient lysis of EGF-R+ tumor cells (A431, HT-29, IGROV-1 and MDA-MB468) by cytotoxic T lymphocytes (CTL) cultured in IL-2. Pretreatment of effector cells by anti-LFA-1 alpha (CD11a) and anti-LFA-1 beta (CD18) MAbs significantly inhibited cytolysis of all types of EGF-R+ tumor cells, while anti-CD2 and anti-VLA-4 MAbs were virtually ineffective. We investigated the expression of adhesion-molecule counter-receptors on tumor target cells by indirect immunofluorescence. HT-29, A431 and MDA-MB 468 tumor cells expressed an ICAM-1+2-3- VCAM-1- LFA-3+ phenotype, while IGROV-1 was ICAM-1-2+3- VCAM-1- LFA-3+. Pre-treatment of A431, HT-29 and MDA-MB468 with anti-ICAM-1 MAb inhibited cytolysis, further supporting the functional involvement of the LFA-1/ICAM adhesion pathway in biMAb-targeted tumor-cell lysis. In addition, treatment of target cells with TNF alpha or IFN gamma for 24 hr increased the expression of ICAM-1 in HT-29, A431 and MDA-MB468 (ICAM-2 was induced on IGROV-1) and also enhanced the sensitivity of these target cells to biMAb-targeted cytotoxicity. These data suggest that up-regulation of ICAM-molecule expression by inflammatory cytokines may increase susceptibility of tumor cells to biMAb-targeted lysis. Anti-LFA-1 MAbs did not significantly inhibit the formation of conjugates between biMAb-coated T lymphocytes and tumor cells. Co-aggregation of LFA-1 molecules with biMAb-bound CD3 molecules resulted in a more sustained and prolonged increase in the intracellular concentration of free Ca++ in CD8+ cultured CTL lines. These findings indicate that in T cells targeted by anti-CD3/anti-TAA biMAb LFA-1 may act as a co-receptor molecule which enhances signal transduction through the CD3/TCR complex.
Antibodies, Bispecific↗
Expression of a wide T cell receptor V beta repertoire in human T lymphocytes derived in vitro from embryonic liver cell precursors.
As shown recently, CD3+/TcR+ functional T lymphocytes can be derived in culture from embryonic liver cell precursors at a gestational age (6-8 weeks) preceding the colonization of the epithelial thymus. In this report, we analyzed the V beta repertoire of T lymphocytes derived from embryonic liver by applying a quantitative reverse transcriptase-polymerase chain reaction technique. To this end, oligonucleotide primers for C alpha or the various human V beta have been used to study both freshly derived embryonic liver cell suspensions and CD3+/TcR+ populations derived after approximately 6 weeks upon stimulation with 1% phytohemagglutinin and culture in 100 units/ml recombinant interleukin-2. In order to exclude possible contaminations with mother-derived T lymphocytes, only T cells displaying both X and Y chromosomal sequences (i.e. derived from male embryos) were further analyzed. While neither C alpha nor the various V beta could be detected in fresh liver cells, C alpha and the large majority of V beta were detected in in vitro cultured populations. The levels of the various V beta expressed by embryo-derived T cells was similar to that detected in adult peripheral blood-derived T lymphocytes. These experiments indicate that the immature liver precursors can potentially give rise in vitro to T cells which express a wide V beta repertoire and may provide a suitable in vitro system for the analysis of the selection processes mediated by either major histocompatibility complex antigen or superantigens.
Antigens, Surface↗
Expression of N-CAM by human renal cell carcinomas correlates with growth rate and adhesive properties.
In the present study we provide evidence for the involvement of N-CAM in the spreading of human renal cell carcinomas (RCC) through the interaction with the subendothelial matrix. We found that in tumor cell lines derived from human RCC the increase of growth rate and the loss of adhesiveness to inert substrate were accompanied by N-CAM expression and by the appearance of specific binding to endothelial heparan sulfate. Indeed, the adhesion of tumor cells to human endothelial cells and heparan sulfate in vitro was inhibited by monoclonal antibodies able to bind and inactivate N-CAM and was abrogated by endothelial cell treatment with heparitinase. Furthermore, when the renal epithelial cell line COS7 was transfected with a cDNA coding for N-CAM a significant increase in the ability to bind both endothelium and heparan sulfate in vitro was observed. Of note, HS complexed with epithelial growth factor could enhance the proliferation of RCC-derived tumor cells; this effect was also achieved by cross-linking of N-CAM at the surface of tumor cells, suggesting that N-CAM could transduce an activation signal across the cell membrane. This was also supported by the finding that N-CAM cross-linking induced a strong calcium mobilization from internal stores and opening of surface calcium channels in such tumor cells. N-CAM was detectable in vivo at the tumor site in the areas of active proliferation, as judged by the coexpression of Ki67 nuclear antigen, and heparan sulfate was present in the wall of blood vessels in the proximity of the tumor. These findings would suggest that growing kidney tumors might use N-CAM to bind the subendothelial matrix and complexed growth factors during tissue invasion and spreading.
Carcinoma, Renal Cell↗