POSITIVE ASSOCIATION BETWEEN CYTOSKELETAL CHANGES, MELANOMA CELL ATTACHMENT AND INVASION IN-VITRO

The literature concerning cytoskeletal changes and metastatic progress ion is unresolved, some studies suggesting a positive association betw een the ability of cells to organize their cytoskeleton and others sug gesting an inverse correlation. In an attempt to learn more about cyto skeletal changes and the ability of melanoma cells to interact with ex tracellular matrix proteins we examined the effects of pharmacological manipulation of cell attachment and cell invasion through fibronectin on levels of F-actin end vimentin in a highly metastatic cutaneous me lanoma cell line (A375-SM cells). Additionally, we examined whether an y correlation existed between the levels of the cytoskeletal proteins and subpopulations of the cell line of varying invasive ability. We re port that agents which reduced cell attachment to plastic and invasion through fibronectin in vitro (tamoxifen, N-desmethyltamoxifen and 17 beta-oestradiol) caused increases in levels of F-actin and vimentin, w hereas agents which did not affect attachment or invasion (4-hydroxyta moxifen and dihydrotestosterone) had little or no effect on the cytosk eletal proteins. In contrast, however, those cells which were most eff ective at invading through fibronectin were significantly better at ac utely increasing their levels of F-actin and vimentin than less invasi ve cells. We speculate that the ability to rapidly and possibly revers ibly alter the cytoskeleton might be associated with metastatically su ccessful cells in vivo. (C) 1998 Lippincott Williams & Wilkins.