Differential effects of phorbol ester on the in vitro invasiveness of malignant and non-malignant human fibroblast cells.
The effect of the phorbol ester tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) on cell invasion was studied using an in vitro assay for cell invasion through a reconstituted basement membrane matrix (Matrigel). TPA inhibited the invasiveness of malignant human fibrosarcoma HT1080 cells. In contrast, WI-38 lung fibroblasts, which show a very low invasive capacity, were stimulated (3-fold) to invade Matrigel after exposure to TPA for 48 hours. The inhibitory or stimulatory effects of TPA on cell invasion were correlated with a decrease or an increase in cell motility and collagenase IV activity, respectively. Synthetic diacylglycerols partially mimicked the inhibitory action of TPA on HT1080 cells but failed to stimulate WI-38 cell invasion. Immunoblots demonstrated that in both cell lines the alpha and beta isoforms of protein kinase C were equally down-regulated after a 5 hour exposure to TPA despite the basal low level of protein kinase C polypeptide in the malignant cells. Thus, whereas in WI-38 cells induction of an invasive behavior could be observed in the absence of protein kinase C, in the malignant cells disappearance of the kinase was associated with a non-invasive phenotype.
Fridman
R
R
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
Lacal
J C
JC
Reich
R
R
Bonfil
D R
DR
Ahn
C H
CH
D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D004075:Diglycerides / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D003012:Microbial Collagenase / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000276:immunology / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D004075:Diglycerides; D010703:Phorbol Esters; D011493:Protein Kinase C; D003012:Microbial Collagenase; D013755:Tetradecanoylphorbol Acetate