The expression of integrin alpha 2 beta 1 and attachment to type I collagen of melanoma cells are preferentially induced by tumour promoter, TPA (12-O-tetradecanoyl phorbol-13-acetate).
The adhesion of melanoma cells to the extracellular matrix (ECM) protein is likely to be essential in their invasive metastatic processes. Treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a potent protein kinase C (PKC) activator, preferentially induced the expression of alpha 2 beta 1 integrin, the receptor for collagen/laminin. The number of cells attached to type I collagen, but not laminin, was increased by treatment with TPA. Prior exposure to PKC inhibitors such as H-7 (20 mumol/l) and calphostin C (50 mumol/l) had no effect on TPA-induced alpha 2 beta 1 integrin expression and cell attachment to type I collagen, whereas prior exposure to the calmodulin antagonist W-7(50 mumol/l) inhibited these TPA-induced events. The augmented adhesion was also inhibited by anti-alpha 2 antibody. These data suggest that the increased attachment of melanoma cells to type I collagen appears to be mediated by the preferential augmentation of integrin alpha 2 beta 1, and the activation of calmodulin kinase, but not via the activation of PKC. Analysis of the expression of integrins and of cell attachment to ECMs is important in elucidating the mechanisms involved in the progression and metastasis of malignant melanoma.
Eguchi
H
H
Department of Dermatology, Sapporo Medical University, Japan.
Horikoshi
T
T
D002273:Carcinogens / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002273:Carcinogens; D019012:Integrin beta1; D003094:Collagen; D013755:Tetradecanoylphorbol Acetate