Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma.
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.
Department of Obstetrics & Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.|Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Yuanyuan
Y
Hua
Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Pui-Wah
PW
Choi
Harvard Catalyst Laboratory for Innovative Translational Technologies, Harvard Medical School, Boston, Massachusetts, USA.
Alexander J
AJ
Trachtenberg
Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Allen C
AC
Ng
Harvard Catalyst Laboratory for Innovative Translational Technologies, Harvard Medical School, Boston, Massachusetts, USA.|Predicine, Inc., Hayward, California, USA.
Winston P
WP
Kuo
School of Medicine and Menzies Health Institute Queensland, Griffith University, Nathan, Australia.
Shu-Kay
SK
Ng
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Daniela M
DM
Dinulescu
Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Martin M
MM
Matzuk
Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ross S
RS
Berkowitz
Department of Obstetrics/Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Shu-Wing
SW
Ng
D000818:Animals; D017209:Apoptosis; D000077216:Carcinoma, Ovarian Epithelial; D002448:Cell Adhesion; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D053487:DEAD-box RNA Helicases / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition; D005187:Fallopian Tubes / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D018345:Mice, Knockout; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D011379:Prognosis; D043244:Ribonuclease III / Q000502:physiology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D053487:DEAD-box RNA Helicases
fallopian tube; ovarian cancer