Tumor autocrine motility factor responses are mediated through cell contact and focal adhesion rearrangement in the absence of new tyrosine phosphorylation in metastatic cells

Steve Silletti, Sandor Paku, Avraham Raz

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Autocrine motility factor (AMF) is a tumor-secreted cytokine that acts as a motogen as well as a mitogen via a receptor-mediated signaling pathway(s). Expression of the AMF receptor (AMF-R) in normal cells is regulated by cell contact whereas in transformed cells AMF-R is constitutively expressed irrespective of cell density. Here we have analyzed the regulation of AMF-R expression in a BALB/c angiosarcoma tumor system that allows investigation of cellular characteristics associated with tumor progression. The metastatic cell variant (A31-M) displayed a higher rate of unstimulated motility and responded to tumor-derived AMF locomotory stimulus as compared with the nonmetastatic cell variants (A31-TR and A31-TU) and, although a similar level of receptor expression was detected in cellular extracts from subconfluent cultures of these sublines, surface localization differed and cell contact down-regulated AMF-R expression in the normal but not the transformed cell counterparts, AMF promoted marked rearrangement of focal adhesion plaque proteins in the AMF migration-responsive cells exclusively. Reorganization of vinculin after AMF stimulation was paralleled by morphological redistribution of tyrosine-phosphorylated proteins and the tyrosine kinase pp125(FAK) in the migration-responsive cells; however, we did not observe a concomitant change in the pp125(FAK) phosphorylation state or the general level of cellular tyrosine phosphorylation in response to treatment, suggesting that the induction of cellular migration by AMF is independent of tyrosine phosphorylation events at the focal contacts and may therefore represent a novel pathway of cytokine-induced migration regulation.

Original languageEnglish
Pages (from-to)1649-1660
Number of pages12
JournalAmerican Journal of Pathology
Issue number5
Publication statusPublished - May 1 1996


ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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