Zeinoun Z, Teugels E, De Bleser P J, Neyns B, Geerts A, De Greve J
Department of Medical Oncology and Hematology, Academisch Ziekenhuis, Vrije Universiteit Brussel, Brussels, Belgium.
Anticancer Res. 1999 Jan-Feb;19(1A):413-20.
TGF-beta 1 is a secreted polypeptide that elicits an antiproliferanve response in many cell types. However, many epithelial cancer cell lines are resistant to TGF-beta 1 growth inhibition. We investigated the in vitro growth suppressive effect of TGF-beta 1 on five ovarian cancer cell lines. Two of these (OVCAR-3 and AZ364) were growth inhibited by TGF-beta 1. The other three cell lines (SKOV-3, AZ224 and AZ547), were resistant to the antiproliferative action of the cytokine. All five cell lines produce TGF-beta 1 mRNA at very different levels and also secrete the TGF-beta 1 polypeptide, but mainly in a biologically latent form as tested by ELISA; this probably explains the fact that the TGF-beta 1 autocrine growth inhibition circuit is not active, even in sensitive cell lines. Even complete activation of the in vitro secreted latent form would be insufficient to induce growth arrest when compared to the levels of exogenous TGF-beta 1 needed to induce growth arrest in sensitive cell lines. The TGF-beta 1 receptor type I mRNA is expressed by all five ovarian cancer cell lines, but two of them (AZ224 and AZ547) lack detectable TGF-beta 1 receptor type II mRNA expression. Since TGF-beta 1 signaling requires both receptor types, the lack of receptor type II in two cell lines may explain their resistance to growth inhibition. Further experiments should be carried out on receptors and downstream components to pinpoint the cause of resistance in the SKOV cell line.
转化生长因子β1（TGF-β1）是一种分泌型多肽，可在多种细胞类型中引发抗增殖反应。然而，许多上皮癌细胞系对TGF-β1的生长抑制具有抗性。我们研究了TGF-β1对五种卵巢癌细胞系的体外生长抑制作用。其中两种细胞系（OVCAR-3和AZ364）受到TGF-β1的生长抑制。另外三种细胞系（SKOV-3、AZ224和AZ547）对该细胞因子的抗增殖作用具有抗性。所有五种细胞系均以非常不同的水平产生TGF-β1 mRNA，并且也分泌TGF-β1多肽，但通过酶联免疫吸附测定（ELISA）检测主要以生物学潜伏形式存在；这可能解释了即使在敏感细胞系中，TGF-β1自分泌生长抑制回路也不活跃这一事实。与在敏感细胞系中诱导生长停滞所需的外源性TGF-β1水平相比，即使完全激活体外分泌的潜伏形式也不足以诱导生长停滞。所有五种卵巢癌细胞系均表达I型TGF-β1受体mRNA，但其中两种细胞系（AZ224和AZ547）缺乏可检测到的II型TGF-β1受体mRNA表达。由于TGF-β1信号传导需要两种受体类型，两种细胞系中缺乏II型受体可能解释了它们对生长抑制的抗性。应针对受体和下游成分进行进一步实验，以查明SKOV细胞系中的抗性原因。
