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

We have examined the expression of 72-kDa gelatinase/type IV collagenase or matrix metalloproteinase-2 (MMP-2) and its inhibitor, tissue inhibitor of metalloproteinase-2 (TIMP-2), in various cell lines derived from paediatric tumours. In a neuroblastoma model system of tumour progression, the expression level of MMP-2 mRNA was higher in the more malignant cell line. Surprisingly, MMP-2 was not expressed in the highly malignant rhabdomyosarcoma A-204 cell line. TIMP-2 showed higher expression levels in the 007 and U-2OS tumour cell lines than in the more malignant ones, WAC2 and A-204 cells. We have also determined the effect of some tumour cell proliferation modulators on gelatinolytic activity. While basic fibroblast growth factor and retinoic acid produced no apparent change in gelatinolytic activity, genistein induced in partial inhibition of gelatinolytic activity.
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PMID:Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 expression in paediatric tumour cells. Effects of tumour cell proliferation modulators on gelatinolytic activity. 776 64

Knowledge on molecular systems involved in myogenic precursor cell (mpc) fusion into myotubes is fragmentary. Previous studies have implicated the a disintegrin and metalloproteinase (ADAM) family in most mammalian cell fusion processes. ADAM12 is likely involved in fusion of murine mpc and human rhabdomyosarcoma cells, but it requires yet unknown molecular partners to launch myogenic cell fusion. ADAM12 was shown able to mediate cell-to-cell attachment through binding alpha9beta1 integrin. We report that normal human mpc express both ADAM12 and alpha9beta1 integrin during their differentiation. Expression of alpha9 parallels that of ADAM12 and culminates at time of fusion. alpha9 and ADAM12 coimmunoprecipitate and participate to mpc adhesion. Inhibition of ADAM12/alpha9beta1 integrin interplay, by either ADAM12 antisense oligonucleotides or blocking antibody to alpha9beta1, inhibited overall mpc fusion by 47-48%, with combination of both strategies increasing inhibition up to 62%. By contrast with blockade of vascular cell adhesion molecule-1/alpha4beta1, which also reduced fusion, exposure to ADAM12 antisense oligonucleotides or anti-alpha9beta1 antibody did not induce detachment of mpc from extracellular matrix, suggesting specific involvement of ADAM12-alpha9beta1 interaction in the fusion process. Evaluation of the fusion rate with regard to the size of myotubes showed that both ADAM12 antisense oligonucleotides and alpha9beta1 blockade inhibited more importantly formation of large (> or =5 nuclei) myotubes than that of small (2-4 nuclei) myotubes. We conclude that both ADAM12 and alpha9beta1 integrin are expressed during postnatal human myogenic differentiation and that their interaction is mainly operative in nascent myotube growth.
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PMID:ADAM12 and alpha9beta1 integrin are instrumental in human myogenic cell differentiation. 1557 85