EFFECTS OF PHORBOL-12-MYRISTATE-13-ACETATE ON PHENOTYPIC PROGRAM OF CULTURED CHONDROBLASTS AND FIBROBLASTS

Abstract

The carcinogen phorbol-12-myristate-13-acetate (PMA) has a prompt, differential and partially reversible effect on cultured chick chondroblasts. Within 36 h PMA transforms sessile, polygonal, epthelioid chondroblasts into motile, multilayered, fibroblastic cells. In PMA chick chondroblasts rapidly cease to synthesize 2 of their terminal luxury molecules, the type IV sulfated proteoglycan that characterizes the extracell matrix and a glycosylated protein with an apparent molecular weight of 180,000. This glycosylated protein constitutes approximately 5% of the total protein in normal chondroblasts. If returned to normal medium after 4 days in PMA, 100% of the cells reinitiate the synthesis of their type IV sulfated proteoglycan, the 180,00-dalton protein and reacquire their polygonal, epithelioid morphology. If returned to normal medium after 12 days in PMA, the cells fail to synthesize their 2 characteristic luxury molecules, and 100% of the cells remain fibroblastic. PMA alters the morphology of chick fibroblasts but does not block synthesis of their characteristic type III sulfated proteoglycan. PMA proves to be a mitogen for chondroblasts but not for fibroblasts, in spite of the phenotypic similarities of these 2 cell types.