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Metastasizing ovarian carcinoma cells encounter a collagen\u2010rich microenvironment because the submesothelial matrix is comprised mainly of interstitial collagens Types I and III.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Immunohistochemistry using primary and metastatic ovarian carcinoma samples was employed to detect expression of Wilms tumor gene protein 1 (WT1). Three\u2010dimensional (3D) collagen culture, real\u2010time reverse transcriptase\u2010polymerase chain reaction, and immunofluorescent staining were used to evaluate changes in WT1 RNA and protein expression in response to 3D collagen culture. Boyden chamber invasion assay, scratch\u2010wound motility assay, and Western blot analysis were used to establish the function of WT1 in ovarian carcinoma cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>To model intraperitoneal invasion in vitro, ovarian cancer cells were cultured in a 3D collagen microenvironment. 3D collagen culture resulted in robust induction of WT1 at the mRNA and protein levels. WT1 expression was prevalent in primary ovarian tumors and was retained in paired peritoneal metastases. Functional studies supported a role for WT1 in intraperitoneal invasion, because siRNA knockdown of WT1 expression reduced the ability of ovarian cancer cells to invade 3D collagen gels.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The data from the current study identify a novel regulatory mechanism for the control of WT1 expression and provide evidence for a functional role of WT1 protein in the control of cellular invasive activity. Cancer 2008. \u00a92008 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.23341","type":"journal-article","created":{"date-parts":[[2008,2,7]],"date-time":"2008-02-07T18:46:40Z","timestamp":1202410000000},"page":"1632-1641","source":"Crossref","is-referenced-by-count":41,"title":["Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasion"],"prefix":"10.1002","volume":"112","author":[{"given":"Maria V.","family":"Barbolina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Adley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonnie D.","family":"Shea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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