Possible angiogenic roles for claudin-4 in ovarian cancer.
Possible angiogenic roles for claudin-4 in ovarian cancer.
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DOI：
10.4161/cbt.8.19.9427
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发表时间：
2009-10
影响因子：
3.6
通讯作者：
Morin PJ
中科院分区：
文献类型：
--
作者：
Li J;Chigurupati S;Agarwal R;Mughal MR;Mattson MP;Becker KG;Wood WH 3rd;Zhang Y;Morin PJ
紧密连接蛋白在各种肿瘤中经常过表达，如乳腺癌、前列腺癌和卵巢癌。虽然它们在癌症中的功能尚未完全阐明，但已提出在存活、粘附和侵袭中的作用。为了阐明claudins在卵巢癌中的作用，我们对过表达claudin-4的卵巢表面上皮细胞进行了基因表达谱分析，并将其表达模式与亲本非表达细胞进行了比较。紧密连接蛋白-4的表达导致了几个基因的差异表达，包括许多以前已经参与血管生成的基因。特别是，血管生成细胞因子，如IL-8，被发现升高，而血管抑制干扰素途径的基因被发现下调。体外测定显示，表达claudin-4的细胞产生可以刺激血管生成的因子，如通过HUVEC细胞中的管形成和迁移所测量的。此外，体内小鼠背侧皮褶测定证实表达密蛋白-4的细胞分泌可介导小鼠背侧皮肤中血管生成的因子。我们的数据表明了claudin-4在癌症中的新功能，并为其在人类肿瘤中的常见过表达提供了额外的理由。
Claudin proteins are frequently overexpressed in various tumors such as breast, prostate and ovarian cancer. While their functions in cancer have not been completely elucidated, roles in survival, adhesion, and invasion have been suggested. In order to clarify the roles of claudins in ovarian cancer, we have performed gene expression profiling of ovarian surface epithelial cells overexpressing claudin-4 and compared the expression patterns to the parental, non-expressing cells. Claudin-4 expression leads to the differential expression of several genes, including many that have previously been implicated in angiogenesis. In particular, angiogenic cytokines, such as IL-8, were found elevated while genes of the angiostatic interferon pathway were found down-regulated. In vitro assays show that claudin-4-expressing cells produce factors that can stimulate angiogenesis as measured by tube formation and migration in HUVEC cells. In addition, an in vivo mouse dorsal skinfold assay confirms that cells expressing claudin-4 secrete factors that can mediate angiogenesis in the dorsal skin of mice. Our data suggest a novel function for claudin-4 in cancer and provide an additional rationale for its common overexpression in human tumors.
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