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首页> 外文期刊>Journal of Cellular Physiology >Desensitization of melanoma cells to autocrine TGF-beta isoforms.
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Desensitization of melanoma cells to autocrine TGF-beta isoforms.

机译：脱敏的黑色素瘤细胞自分泌鉴定及亚型。

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摘要

Previous studies have suggested that transforming growth factor-beta 1 (TGF-beta1) acts as an autocrine growth inhibitor on normal human melanocytes, while melanoma cells may not respond to this stimulus. The role of other TGF-beta isoforms such as TGF-beta2 and TGF-beta3 remained less well characterized. In the present study, the mRNA and protein levels of all three isoforms of TGF-beta were analyzed in a panel of human melanoma cell lines and in cultures of normal human melanocytes in vitro. Northern analysis showed that the degree of TGF-beta1, -beta2, -beta3 mRNA expression varied considerably in melanoma cells, whereas TGF-beta expression was very low in melanocytes. In melanoma cells, secreted amounts of TGF-beta1 and TGF-beta3 were found increased in comparison to normal melanocytes: 615 pg/ml vs. 118 pg/ml and 193 pg/ml vs. 30 pg/ml (mean values). In addition, low levels of TGF-beta2 were detected (mean value: 28 pg/ml). Although TGF-beta secretion increased, the proliferation of melanoma cells was found to be only moderately inhibited by TGF-beta isoforms, in contrast to its strong antiproliferative effect on normal human melanocytes: - 15%, -11%, and -18% vs. -52%, -46%, and -50% average inhibition at 0.5 ng/ml TGF-beta1, -beta2, and -beta3, respectively. The different efficacy of TGF-beta on melanocyte and melanoma cells was highly significant (P<0.0001); in addition, TGF-beta-dependent growth inhibition of melanoma cells from primary tumors vs. cells from metastases showed a trend for further decreased response for the metastatic populations (P< or = 0.075). Measurements of DNA synthesis revealed even more pronounced differences between melanocytes (-86%, -78%, and -80% inhibition, respectively, for TGF-beta1, -beta2, and -beta3) and melanoma cells (no inhibition). Our data show loss of responsiveness of melanoma cells to the growth-inhibitory function of TGF-beta isoforms but not of melanocytes. Although melanoma cells are not growth-inhibited by all three TGF-beta isoforms, they secrete significantly higher levels of TGF-beta, as compared to melanocytes. The reduced response indicates their escape from TGF-beta surveillance with ongoing tumor progression.
机译：先前的研究已经表明,改造生长因子1 (TGF-beta1)充当自分泌生长抑制剂在正常的人类黑色素细胞,黑色素瘤细胞可能没有回应这种刺激。亚型TGF-beta2和TGF-beta3等依然存在少的特点。信使rna和蛋白质水平的所有三个亚型的鉴定及分析了人类黑素瘤细胞系和正常的文化人类黑色素细胞体外。显示的程度TGF-beta1 beta2,- beta3 mRNA表达差异黑素瘤细胞,而鉴定及表达式非常低的黑色素细胞。分泌大量TGF-beta1和TGF-beta3发现增加比较正常黑色素细胞:615 pg / ml vs 118 pg / ml和193年pg / ml和30 pg / ml(平均值)。低水平的TGF-beta2检测(的意思价值:28 pg / ml)。增加,黑色素瘤细胞的增殖被发现只有适度抑制及亚型,相比之下其强劲抗增殖影响正常的人类黑色素细胞:15%,-11%,-18%和-52%,-46%和-50%平均抑制0.5 ng / ml分别TGF-beta1、beta2 - beta3。不同的鉴定及黑素细胞和功效黑色素瘤细胞是高度显著(P < 0.0001);此外,TGF-beta-dependent抑制增长黑素瘤细胞从原发肿瘤和细胞进一步显示转移的趋势减少人口转移的反应(P < = 0.075)。显示之间的差异更加明显抑制黑色素细胞(-86%、-78%和-80%,分别为TGF-beta1 beta2和- beta3)和黑色素瘤细胞(无抑制)。黑色素瘤细胞的响应能力的损失growth-inhibitory功能及亚型但不是黑色素细胞。不是由所有三个growth-inhibited及护吗亚型,它们分泌显著提高水平的鉴定及黑色素细胞相比。减少的反应表明他们逃离及监控与持续的肿瘤进展。

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