Ligands to FGF receptor 2-IIIb induce proliferation, motility, protection from cell death and cytoskeletal rearrangements in epithelial ovarian cancer cell lines
Ligands to FGF receptor 2-IIIb induce proliferation, motility, protection from cell death and cytoskeletal rearrangements in epithelial ovarian cancer cell lines
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DOI：
10.1080/08977190500361697
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发表时间：
2006-03-01
期刊：
影响因子：
1.8
通讯作者：
Davies, BR
中科院分区：
文献类型：
--
作者：
Steele, IA;Edmondson, RJ;Davies, BR
上皮性卵巢癌(EOC)是妇科最常见、最致命的恶性肿瘤。这些癌症被认为起源于卵巢表面上皮(OSE)。我们以前曾报道，上皮特异性的成纤维细胞生长因子受体2剪接变异体IIIb在正常OSE中不表达，但在大约80%的EOCs中表达。我们研究了成纤维细胞生长因子受体2-IIIb的配体，即成纤维细胞生长因子1、7和10在一组卵巢癌细胞系上的表型效应。我们发现，当EOC细胞在无血清介质中维持时，这些配体可以提高细胞活力，诱导DNA合成、运动和趋化，并防止细胞自发性死亡。封闭的抗成纤维细胞生长因子-7血清降低了41-M EOC细胞的活力，并取消了含有成纤维细胞生长因子-7的腹水诱导这些细胞DNA合成的能力。最后，我们发现成纤维细胞生长因子-7可以诱导SK-OV-3卵巢癌细胞肌动蛋白细胞骨架的重组。提示成纤维细胞生长因子受体2-IIIb的配体影响一系列在EOCs肿瘤生长中重要的表型。
Epithelial ovarian cancer (EOC) is the most common and lethal form of gynecological malignancy. These cancers are thought to be derived from the ovarian surface epithelium (OSE). We have previously reported that the epithelial-specific FGF receptor 2 splice variant IIIb is not expressed in normal OSE, but is expressed in approximately 80% of EOCs. We have examined the phenotypic effects of ligands to FGF receptor 2-IIIb, namely FGFs 1,7 and 10, on a panel of EOC cell lines. We show that these ligands increase cell viability, induce DNA synthesis, motility and chemotaxis and protect from spontaneous cell death when EOC cells are maintained in serum free medium. A blocking antiserum to FGF-7 reduces viability of 41-M EOC cells, and abrogates the ability of ascitic fluid containing FGF-7 to induce DNA synthesis in these cells. Finally, we show that FGF-7 can induce a reorganization of the actin cytoskeleton in SK-OV-3 ovarian cancer cells. It is suggested that ligands to FGF receptor 2-IIIb affect a range of phenotypes important in the neoplastic growth of EOCs.