TUMOR PROMOTER-INDUCED MEMBRANE-BOUND PROTEIN KINASE-C REGULATES HEMATOGENOUS METASTASIS
TUMOR PROMOTER-INDUCED MEMBRANE-BOUND PROTEIN KINASE-C REGULATES HEMATOGENOUS METASTASIS
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DOI：
10.1073/pnas.85.2.612
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发表时间：
1988-01-01
影响因子：
11.1
通讯作者：
BARSKY, SH
中科院分区：
文献类型：
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作者：
GOPALAKRISHNA, R;BARSKY, SH
经静脉注射后，膜结合蛋白激酶C的基础水平与B16黑色素瘤细胞亚群（F10、F1和BL6）转移到肺部的能力之间存在很强的相关性。通过用促肿瘤磷酸酯治疗1小时，低转移性F1细胞表现出蛋白激酶C从细胞质溶胶向质膜的易位，并且转移增加到与（未治疗的）高转移亚群F10相当的水平。用12-肉豆蔻酸13-醋酸佛波延长治疗黑色素瘤亚群24小时，导致蛋白激酶C活性失活和其转移能力丧失。在仅诱导蛋白激酶C激活而不诱导其膜结合的条件下，未发生转移增加，提示仅激活蛋白激酶C不足以促进转移，其膜结合也是必要的。将B16黑色素瘤亚群暴露于磷酯1小时(i)对这些细胞在体内和体外的生长和形态没有影响，（ii）有短期影响（.apprxeq）。然而，在这一时期，膜结合蛋白激酶C可能通过影响细胞表面和细胞附着特性，增加了循环黑色素瘤细胞在肺中的滞留，最终导致转移结节数量增加。膜结合蛋白激酶C活性也与快速生长细胞、生长停滞细胞和低ca2 +培养基中生长的细胞的转移能力相关。结果强烈提示膜结合蛋白激酶C影响肿瘤细胞的血行转移，并表明肿瘤启动子如佛博尔酯在促进肿瘤在体内的血行转移中具有额外的作用。
A strong correlation was found between the basal levels of membrane-bound protein kinase C and the ability of B16 melanoma cell sublines (F10, F1, and BL6) to metastasize to the lung after intravenous injection. By treating with tumor-promoting phorbol esters for 1 hr, the low-metastasizing F1 cells exhibited both translocation of protein kinase C from cytosol to plasma membrane and an increase in metastasis to a level comparable to the (untreated) highly metastatic subline F10. Prolonged treatment of melanoma sublines with phorbol 12-myristate 13-acetate for 24 hr resulted in both inactivation of protein kinase C activity and loss of their metastasizing capabilities. Under conditions that induced only the activation of protein kinase C but not its membrane association, no increase in metastasis occurred, suggesting that activation of protein kinase C alone is insufficient to promote metastasis and that its membrane association is also necessary. Exposure of B16 melanoma sublines to phorbol esters for 1 hr had (i) no effect on the growth and morphology of these cells in vivo and in vitro and (ii) a short-term effect (.apprxeq. 5 hr) on membrane association of protein kinase C. Nonetheless, in this period, the membrane-bound protein kinase C, probably by influencing cell-surface and cell-attachment properties, increased the retention of circulating melanoma cells in the lung, which eventually led to an increased number of metastatic nodules. The membrane-bound protein kinase C activity also correlated with metastatic ability in rapidly growing cells, growth-arrested cells, and cells growing in a low-Ca2+ medium. The results strongly suggest that the membrane-bound protein kinase C influences hematogenous metastasis of tumor cells and show that tumor promoters like phorbol esters have an additional role in promoting hematogenous spread of cancer in the body.