Oncotarget

Research Papers:

Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

Yuanyuan Hua _, Pui-Wah Choi, Alexander J. Trachtenberg, Allen C. Ng, Winston P. Kuo, Shu-Kay Ng, Daniela M. Dinulescu, Martin M. Matzuk, Ross S. Berkowitz and Shu-Wing Ng

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Oncotarget. 2016; 7:66077-66086. https://doi.org/10.18632/oncotarget.11808

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Abstract

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

Correspondence to:

Shu-Wing Ng, email: sng@partners.org

Keywords: ovarian cancer, fallopian tube

Received: May 11, 2016    Accepted: August 13, 2016    Published: September 01, 2016

ABSTRACT

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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