Interleukin-6 and 12-O-tetradecanoyl phorbol-13-acetate act synergistically in inducing cell-cell separation and migration of human breast carcinoma cells.
Interleukin-6 and 12-O-tetradecanoyl phorbol-13-acetate act synergistically in inducing cell-cell separation and migration of human breast carcinoma cells.
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DOI：
10.1016/1043-4666(91)90019-a
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发表时间：
1991-05
期刊：
影响因子：
3.8
通讯作者：
I. Tamm;I. Cardinale;P. Sehgal
中科院分区：
文献类型：
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作者：
I. Tamm;I. Cardinale;P. Sehgal
白细胞介素-6 （IL-6）引起人导管乳腺癌细胞系ZR-75-1和T-47D上皮细胞向成纤维细胞样细胞转化并增加运动性。虽然IL-6降低了这些细胞系的DNA合成活性，但IL-6诱导的细胞形状和运动的改变与DNA合成本身的抑制无关。尽管肿瘤坏死因子α (TNF-α)抑制T-471细胞中的DNA合成，但它不会引起上皮-成纤维样细胞转化或其他主要形态学变化，也不会增加细胞的运动能力；TNF-α迅速溶解大部分ZR-75-1细胞。此外，DNA合成抑制剂5-氟-2 ' -脱氧尿苷（FUDR）和甲氨蝶呤（MTX）也不会引起模仿IL-6对细胞结构和运动的作用。转化生长因子α和β1、酸性和碱性成纤维细胞生长因子、表皮生长因子和胰岛素样生长因子-1 （TGF-α、TGF-β1、aFGF、bFGF、EGF和IGF-1）对乳腺癌细胞形态的影响很小或没有影响，这就排除了IL-6诱导这些生长因子变化的可能性。12- o -十四烷醇磷酸-13-乙酸酯（TPA）诱导ZR-75-1细胞形态和结合行为的变化，而不是8-溴腺苷3 ',5 ' -环单磷酸（Br-cAMP），这些变化与IL-6引起的变化相似但不完全相同。tpa诱导的改变不被抗il -6中和抗体阻断；staurosporine抑制tpa诱导的细胞改变，但对IL-6诱导的细胞改变无抑制作用。IL-6和TPA一起使用的表型效应大大超过单独使用任何一种药物，并在不到1天的时间内导致广泛的细胞散射。这些发现与IL-6和TPA通过独立的途径诱导相似的形态学改变和细胞散射的假设一致。
Interleukin-6 (IL-6) causes an epithelial to fibroblastoid conversion and an increase in the motility of human ductal breast carcinoma cell lines ZR-75-1 and T-47D. Although IL-6 decreases DNA synthetic activity in these cell lines, the IL-6-induced alterations in cell shape and motility occur independently of inhibition of DNA synthesis per se. Whereas tumor necrosis factor α (TNF-α) inhibits DNA synthesis in T-471) cells, it does not cause an epithelial-fibroblastoid conversion or other major morphological changes and does not increase cell motility; TNF-α rapidly lyses a majority of ZR-75-1 cells. Furthermore, the DNA synthesis inhibitors 5-fluoro-2′-deoxyuridine (FUDR) and methotrexate (MTX) also do not cause effects mimicking the action of IL-6 on cell structure and motility. Transforming growth factors α and β1, acidic and basic fibroblast growth factors, epidermal growth factor, and insulin-like growth factor-1 (TGF-α, TGF-β1, aFGF, bFGF, EGF, and IGF-1) have little or no effect on breast cancer cell morphology, which serves to exclude the possibility that the IL-6-induced changes are a consequence of induction of these growth factors by IL-6. 12-O-tetradecanoyl phorbol-13-acetate (TPA) but not 8-bromoadenosine 3′,5′-cyclic monophosphate (Br-cAMP) induces changes in the morphology and associative behavior of ZR-75-1 cells that are similar but not identical to those caused by IL-6. The TPA-induced alterations are not blocked by anti-IL-6 neutralizing antibodies; staurosporine inhibits the TPA-induced cell alterations but not those induced by IL-6. IL-6 and TPA used together have a phenotypic effect that greatly exceeds that of either agent alone and results in extensive cell scattering in less than 1 day. These findings are consistent with the hypothesis that IL-6 and TPA induce similar morphological changes and cell scattering via independent pathways.