It has recently been suggested by several investigators that the epithelial-mesenchymal transition-inducing capacity of TGFbetas contributes to invasive transition of tumors at later stages of carcinogenesis. In the present study, we examined the possibility of TGFbeta1-stimulated epithelial-mesenchymal transition in SiHa cell line, detailed molecular events in the process, and its possible contribution to the invasive transition of tumors. TGFbeta1-induced epithelial-mesenchymal transition of SiHa cells was based on morphological and biochemical criteria; actin stress fiber formation, focal translocalization of integrin alphav, talin, and vinculin, fibronectin-based matrix assembly at the cell periphery, and translocalization and down-regulation of E-cadherin. TGFbeta1 also stimulated surface expression of integrin alphavbeta3 and FAK activation. Focal translocalization of integrin alphav preceded actin reorganization and fibronectin matrix assembly, and functional blocking of the integrin suppressed actin stress fiber formation. Furthermore, induction of actin reorganization and fibronectin matrix assembly by TGFbeta1 were shown to be mutually independent events. These changes were irreversible because 5 minutes pulse exposure to TGFbeta1 was sufficient to stimulate progress of actin reorganization and fibronectin matrix assembly. In further studies with raft culture, TGFbeta1 was found to stimulate invasion of SiHa cells into a type I collagen gel matrix. In conclusion, TGFbeta1 stimulated epithelial-mesenchymal transition of SiHa cells, indicating a positive role in the invasive transition of tumors.

中文翻译：

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TGFbeta1介导的上皮到间质转化伴随着SiHa细胞系的侵袭。

几位研究者最近建议，TGFβ的上皮-间充质转化诱导能力有助于在癌变的后期侵入性转化肿瘤。在本研究中，我们检查了SiHa细胞系中TGFbeta1刺激的上皮-间充质转化的可能性，该过程中的详细分子事件及其对肿瘤侵袭性转化的可能贡献。TGFbeta1诱导的SiHa细胞上皮-间质转化基于形态学和生化指标；肌动蛋白应激纤维形成，整联蛋白αv，塔林和新蛋白的局灶性转位，细胞周围基于纤连蛋白的基质组装以及E-钙粘蛋白的转位和下调。TGFbeta1还刺激整联蛋白alphavbeta3和FAK激活的表面表达。整合素αv的局部转位在肌动蛋白重组和纤连蛋白基质组装之前发生，并且对整合素的功能性阻断抑制了肌动蛋白应力纤维的形成。此外，TGFbeta1诱导肌动蛋白重组和纤连蛋白基质组装是相互独立的事件。这些变化是不可逆的，因为5分钟脉冲暴露于TGFbeta1足以刺激肌动蛋白重组和纤连蛋白基质组装的进展。在筏式培养的进一步研究中，发现TGFbeta1刺激SiHa细胞侵入I型胶原凝胶基质。总之，TGFbeta1刺激了SiHa细胞的上皮-间质转化，表明在肿瘤的侵袭性转化中发挥了积极作用。