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Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasion
Article first published online: 7 FEB 2008
Copyright © 2008 American Cancer Society
Volume 112, Issue 7, pages 1632–1641, 1 April 2008
How to Cite
Barbolina, M. V., Adley, B. P., Shea, L. D. and Stack, M. S. (2008), Wilms tumor gene protein 1 is associated with ovarian cancer metastasis and modulates cell invasion. Cancer, 112: 1632–1641. doi: 10.1002/cncr.23341
- Issue published online: 19 MAR 2008
- Article first published online: 7 FEB 2008
- Manuscript Accepted: 26 OCT 2007
- Manuscript Revised: 16 OCT 2007
- Manuscript Received: 1 AUG 2007
- 2005–2006 Penny Severns Breast
- Cervical and Ovarian Cancer Fund
- Illinois Department of Public Health
- 2006 Ovarian Cancer Research Foundation Program of Excellence award
- National Cancer Institute Research. Grant Number: RO1 CA86984
- ovarian carcinoma;
- Wilms tumor gene protein 1 (WT1);
- 3-dimensional collagen;
- tumor microenvironment;
Although metastatic disease is the primary cause of death from epithelial ovarian carcinoma, to the authors' knowledge the cellular mechanisms that regulate intraperitoneal metastasis are largely unknown. Metastasizing ovarian carcinoma cells encounter a collagen-rich microenvironment because the submesothelial matrix is comprised mainly of interstitial collagens Types I and III.
Immunohistochemistry using primary and metastatic ovarian carcinoma samples was employed to detect expression of Wilms tumor gene protein 1 (WT1). Three-dimensional (3D) collagen culture, real-time reverse transcriptase-polymerase 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-wound motility assay, and Western blot analysis were used to establish the function of WT1 in ovarian carcinoma cells.
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.
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. ©2008 American Cancer Society.