Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma
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Yuanyuan Hua1,2, Pui-Wah Choi2, Alexander J. Trachtenberg3, Allen C. Ng2, Winston P. Kuo3,4, Shu-Kay Ng5, Daniela M. Dinulescu6, Martin M. Matzuk7, Ross S. Berkowitz2, Shu-Wing Ng2
1Department of Obstetrics & Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China
2Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
3Harvard Catalyst Laboratory for Innovative Translational Technologies, Harvard Medical School, Boston, Massachusetts, USA
4Predicine, Inc., Hayward, California, USA
5School of Medicine and Menzies Health Institute Queensland, Griffith University, Nathan, Australia
6Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA
7Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA
Shu-Wing Ng, email: firstname.lastname@example.org
Keywords: ovarian cancer, fallopian tube
Received: May 11, 2016 Accepted: August 13, 2016 Published: September 01, 2016
Epithelial ovarian carcinoma accounts for 90% of all ovarian cancer and is the most deadly gynecologic malignancy. Recent studies have suggested that fallopian tube fimbriae can be the origin of cells for high-grade serous subtype of epithelial ovarian carcinoma (HGSOC). A mouse HGSOC model with conditional Dicer-Pten double knockout (Dicer-Pten DKO) developed primary tumors, intriguingly, from the fallopian tube stroma. We examined the growth and epithelial phenotypes of the Dicer-Pten DKO mouse tumor cells contributable by each gene knockout. Unlike human ovarian epithelial cancer cells that expressed full-length E-cadherin, the Dicer-Pten DKO stromal tumor cells expressed cleaved E-cadherin fragments and metalloproteinase 2, a mixture of epithelial and mesenchymal markers. Although the Dicer-Pten DKO tumor cells lost the expression of mature microRNAs as expected, they showed high levels of tRNA fragment expression and enhanced AKT activation due to the loss of PTEN function. Introduction of a Dicer1-expressing construct into the DKO mouse tumor cells significantly reduced DNA synthesis and the cell growth rate, with concurrent diminished adhesion and ZO1 epithelial staining. Hence, it is likely that the loss of Dicer promoted mesenchymal-epithelial transition in fallopian tube stromal cells, and in conjunction with Pten loss, further promoted cell proliferation and epithelial-like tumorigenesis.
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