Involvement of αvβ3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix
Involvement of αvβ3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix
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DOI：
10.1002/ijc.10433
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发表时间：
2002-06-20
影响因子：
6.4
通讯作者：
Darbeida, H
中科院分区：
文献类型：
--
作者：
Carreiras, F;Thiebot, B;Darbeida, H
像大多数肿瘤细胞一样，卵巢癌细胞的生长严重依赖于它们的新生血管。导致卵巢肿瘤细胞与血管周围的内皮细胞外基质相互作用的黏附分子和细胞事件很难确定。为了了解αvbeta3整合素及其配体纤维连接蛋白在这一过程中的作用，我们采用了IGROVI人卵巢腺癌细胞株和人脐静脉内皮细胞(HUVEC)的体外共培养模型。黏附实验显示IGROVI细胞对HUVEC-ECM有很强的黏附能力。在这一事件中，αvbeta3主要参与并似乎与alpha5beta1整合素协同作用。免疫荧光染色显示IGROVI细胞在细胞下层接触区黏附于HUVEC-ECM上存在αvbeta3和alpha5beta1。此外，我们的数据显示IGROVI细胞中没有纤维连接蛋白染色，并且在IGROVI细胞的影响下，HUVEC-ECM纤维连接蛋白网络被破坏。在卵巢肿瘤组织中的原位实验证实了肿瘤中没有纤维连接蛋白，并且在血管系统中有很强的检测。这些结果提示，在IGROVI细胞与HUVEC-ECM黏附过程中，整合素αvbeta3和alpha5beta1的积极参与和内皮纤维连接蛋白的重组，而IGROVI细胞似乎不能合成纤维连接蛋白。因此，卵巢肿瘤细胞表达的纤维连接蛋白整合素受体和内皮纤维连接蛋白可能在卵巢癌新生血管形成和肿瘤-血管相互作用中起重要作用。(C)2002年Wiley-Liss，Inc.
Like the majority of tumor cells, ovarian cancer cell growth is critically dependent on their neovascularization. Adhesion molecules and cellular events that lead to ovarian tumor cell interactions with endothelial extracellular matrix surrounding the vasculature are poorly identified. To understand the role of alphavbeta3 integrin and its ligand fibronectin in this process, we used in vitro coculture models with IGROVI human ovarian adenocarcinoma cell line and human umbilical vein endothelial cells (HUVEC). Adhesion assays revealed a strong ability of IGROVI cells to adhere to HUVEC-ECM. alphavbeta3 is mainly implicated and seems to cooperate with alpha5beta1 integrin in this event. Immunofluorescence staining revealed the presence of alphavbeta3 and alpha5beta1 in IGROVI cells adhering on HUVEC-ECM at regions of cell sub-stratum contacts. Furthermore, our data showed the absence of fibronectin staining in IGROVI cells and the disruption of the HUVEC-ECM fibrillar fibronectin network under IGROVI cell influence. In situ experiments in ovarian neoplastic tissue corroborated the absence of fibronectin in the tumor and its strong detection in vasculature. These findings suggest the active participation of alphavbeta3 and alpha5beta1 integrins and the reorganization of endothelial fibronectin during the adhesion of IGROVI cells to HUVEC-ECM whereas IGROVI cells seem to be unable to synthesize fibronectin. Thus, fibronectin integrin receptors expressed by ovarian tumor cells and endothelial fibronectin may be of importance in ovarian carcinoma neovascularization and during tumor-vasculature interactions. (C) 2002 Wiley-Liss, Inc.