Fridman R, Lacal J C, Reich R, Bonfil D R, Ahn C H
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, NIH, Bethesda, Maryland 20892.
J Cell Physiol. 1990 Jan;142(1):55-60. doi: 10.1002/jcp.1041420108.
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.
使用一种体外检测方法，通过重组基底膜基质（基质胶）研究佛波酯肿瘤促进剂12 - O - 十四酰佛波醇13 - 乙酸酯（TPA）对细胞侵袭的影响。TPA抑制人恶性纤维肉瘤HT1080细胞的侵袭性。相比之下，侵袭能力非常低的WI - 38肺成纤维细胞在暴露于TPA 48小时后被刺激（提高3倍）侵袭基质胶。TPA对细胞侵袭的抑制或刺激作用分别与细胞运动性和IV型胶原酶活性的降低或增加相关。合成二酰甘油部分模拟了TPA对HT1080细胞的抑制作用，但未能刺激WI - 38细胞侵袭。免疫印迹表明，在两种细胞系中，尽管恶性细胞中蛋白激酶C多肽的基础水平较低，但在暴露于TPA 5小时后，蛋白激酶C的α和β亚型均同等程度地下调。因此，虽然在WI - 38细胞中，在没有蛋白激酶C的情况下可观察到侵袭行为的诱导，但在恶性细胞中，该激酶的消失与非侵袭性表型相关。
