Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To characterize VLA alpha subunit cytoplasmic domain functions, unaltered alpha 2 cDNA (called X2C2) and two chimeric cDNAs (called X2C5 and X2C4) were constructed with extracellular alpha 2 domains and cytoplasmic alpha 2, alpha 5, and alpha 4 domains respectively. Upon transfection into rhabdomyosarcoma (RD) cells, each construct yielded comparable expression levels, immunoprecipitation profiles, and avidity for collagen and laminin. However, while RDX2C2 and RDX2C5 transfectants mediated collagen gel contraction, RDX2C4 and a mock transfectant (RDpF) did not. Conversely, only RDX2C4 cells (but not RDX2C2 or RDX2C5) showed enhanced cell migration on collagen and laminin compared with RDpF cells. This indicates markedly differing roles for integrin alpha subunit cytoplasmic domains in post-ligand binding events. Furthermore, stable exertion of physical force (collagen gel contraction) may involve fundamentally different cellular machinery than the transient adhesion occurring during cell migration. Finally, these findings provide insight into a functional flexibility perhaps resulting from multiple integrins binding to identical ligands.
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PMID:Distinct cellular functions mediated by different VLA integrin alpha subunit cytoplasmic domains. 154 2

Various beta 1 integrins (VLA-2, VLA-3, VLA-4) have been suggested to bind directly to themselves or to each other, thus mediating cell-cell adhesion. Here we expressed the human alpha 2 and alpha 3 subunits in three different cell lines (human erythroleukemia K562, human rhabdomyosarcoma RD and Chinese hamster ovary CHO cells). Although cell surface alpha 2 beta 1 and alpha 3 beta 1 in the transfectants mediated adhesion to matrix ligands (collagen or laminin 5, respectively), in no case did we observe enhanced cell-cell adhesion. In the presence of a range of different divalent cation concentrations, stimulatory anti-beta 1 antibodies or anti-alpha 3 antibodies, VLA-2 and VLA-3 still did not appear to interact directly, through either heterophilic (i.e. VLA-3/VLA-2) or homophilic (i.e. VLA-3/VLA-3) mechanisms, to mediate cell-cell adhesion. Furthermore, in some but not all alpha 3 transfectants we observed an unexpected decrease in cell-cell adhesion, suggesting a novel anti-adhesive function. This inhibitory effect was not observed for alpha 2 transfection nor when the alpha 3 cytoplasmic tail was exchanged with that of another integrin alpha subunit. Finally, no evidence for VLA-4/VLA-4 mediated cell-cell adhesion was observed using alpha 4-transfected K562 and CHO cells. In conclusion, using many different combinations of cell lines, we found that cell-cell adhesion mediated by direct integrin/integrin interaction is not a widespread phenomenon, and is not observable in standard cell-cell adhesion assays. Furthermore, in some cell combinations, alpha 3 expression may actually cause diminished cell-cell adhesion.
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PMID:Investigation of the role of beta 1 integrins in cell-cell adhesion. 858 74

Matrix metalloprotease-2 (MMP-2) plays a pivotal role in cancer invasion and metastasis. Invasive human rhabdomyosarcoma cells (RD) secrete proMMP-2. We recently reported that anti-alpha3 integrin antibody induced the activated form of MMP-2 and enhanced proMMP-2 secretion by RD cells with concomitant enhancement of RD cell invasion. Since recent studies showed that calreticulin interacts with integrin alpha subunit, we hypothesized that calreticulin may be involved in signal transduction of anti-alpha3 integrin antibody-mediated MMP-2 secretion and activation. Here we demonstrate that anti-alpha3 integrin antibody induced a transient enhanced interaction of calreticulin with alpha3 integrin. Transfection of antisense oligonucleotides of calreticulin in RD cells abrogated the interaction between calreticulin and alpha3 integrin, and completely suppressed activation of MMP-2 and enhanced secretion of proMMP-2 induced by anti-alpha3 integrin antibody. Transient overexpression of calreticulin cDNA in RD cells significantly increased secretion of proMMP-2. The results demonstrate for the first time that calreticulin is directly involved in MMP-2 secretion and activation.
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PMID:Calreticulin is directly involved in anti-alpha3 integrin antibody-mediated secretion and activation of matrix metalloprotease-2. 1132 97