Differential effects of phorbol ester on the in vitro invasiveness of malignant and non-malignant human fibroblast cells

✍ Scribed by Rafael Fridman; Juan Carlos Lacal; Reuven Reich; Daniel R. Bonfil; Chang-Ho Ahn

• Publisher: John Wiley and Sons
• Year: 1990
• Tongue: English
• Weight: 694 KB
• Volume: 142
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041420108

✦ Synopsis

The effect of the phorbol ester tumor promoter 12-0-tetradecanoylphorbol 13acctatc (TF'A) 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 HTI 080 cells. In contrast, WI-38 lung fibroblasts, which show a very low invasive capacity, were stimulated (3fold) 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 LVl-38 cell invasion. lmrnunoblots demonstrated that in both cell lines the a and p 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 thc kinase was associated with a non-invasive phenotype.