TY - JOUR

T1 - Positive association between cytoskeletal changes, melanoma cell attachment and invasion in vitro

AU - Dewhurst, L. O.

AU - Rennie, I. G.

AU - MacNeil, S.

PY - 1998/8

Y1 - 1998/8

N2 - The literature concerning cytoskeletal changes and metastatic progression is unresolved, some studies suggesting a positive association between the ability of cells to organize their cytoskeleton and others suggesting an inverse correlation. In an attempt to learn more about cytoskeletal changes and the ability of melanoma cells to interact with extracellular matrix proteins we examined the effects of pharmacological manipulation of cell attachment and cell invasion through fibronectin on levels of F-actin and vimentin in a highly metastatic cutaneous melanoma cell line (A375-SM cells). Additionally, we examined whether any correlation existed between the levels of the cytoskeletal proteins and subpopulations of the cell line of varying invasive ability. We report that agents which reduced cell attachment to plastic and invasion through fibronectin in vitro (tamoxifen, N-desmethyltamoxifen and 17beta-oestradiol) caused increases in levels of F-actin and vimentin, whereas agents which did not affect attachment or invasion (4-hydroxytamoxifen and dihydrotestosterone) had little or no effect on the cytoskeletal proteins. In contrast, however, those cells which were most effective at invading through fibronectin were significantly better at acutely increasing their levels of F-actin and vimentin than less invasive cells. We speculate that the ability to rapidly and possibly reversibly alter the cytoskeleton might be associated with metastatically successful cells in vivo.

AB - The literature concerning cytoskeletal changes and metastatic progression is unresolved, some studies suggesting a positive association between the ability of cells to organize their cytoskeleton and others suggesting an inverse correlation. In an attempt to learn more about cytoskeletal changes and the ability of melanoma cells to interact with extracellular matrix proteins we examined the effects of pharmacological manipulation of cell attachment and cell invasion through fibronectin on levels of F-actin and vimentin in a highly metastatic cutaneous melanoma cell line (A375-SM cells). Additionally, we examined whether any correlation existed between the levels of the cytoskeletal proteins and subpopulations of the cell line of varying invasive ability. We report that agents which reduced cell attachment to plastic and invasion through fibronectin in vitro (tamoxifen, N-desmethyltamoxifen and 17beta-oestradiol) caused increases in levels of F-actin and vimentin, whereas agents which did not affect attachment or invasion (4-hydroxytamoxifen and dihydrotestosterone) had little or no effect on the cytoskeletal proteins. In contrast, however, those cells which were most effective at invading through fibronectin were significantly better at acutely increasing their levels of F-actin and vimentin than less invasive cells. We speculate that the ability to rapidly and possibly reversibly alter the cytoskeleton might be associated with metastatically successful cells in vivo.

KW - Actins

KW - Antineoplastic Agents, Hormonal

KW - Cell Adhesion

KW - Cytoskeletal Proteins

KW - Cytoskeleton

KW - Dihydrotestosterone

KW - Embryonal Carcinoma Stem Cells

KW - Estradiol

KW - Fibronectins

KW - Gene Expression Regulation, Neoplastic

KW - Gonadal Steroid Hormones

KW - Humans

KW - Melanocytes

KW - Melanoma

KW - Neoplasm Invasiveness

KW - Neoplasm Proteins

KW - Neoplastic Stem Cells

KW - Skin Neoplasms

KW - Tamoxifen

KW - Tumor Cells, Cultured

KW - Vimentin

M3 - Journal article

C2 - 9764805

VL - 8

SP - 303

EP - 311

JO - Melanoma Research

JF - Melanoma Research

SN - 0960-8931

IS - 4

ER -