scholarly journals Loss of PAX8 in high-grade serous ovarian cancer reduces cell survival despite unique modes of action in the fallopian tube and ovarian surface epithelium

Oncotarget ◽  
2016 ◽  
Vol 7 (22) ◽  
pp. 32785-32795 ◽  
Author(s):  
Laura H. Rodgers ◽  
Eoghainín Ó hAinmhire ◽  
Alexandria N. Young ◽  
Joanna E. Burdette
Keyword(s):  
Ovarian Cancer ◽  
Cell Survival ◽  
Fallopian Tube ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Modes Of Action ◽  
Ovarian Surface

scholarly journals UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 262 ◽  
Author(s):  
Laura Hardy ◽  
Amrita Salvi ◽  
Joanna Burdette
Keyword(s):  
Ovarian Cancer ◽  
Fallopian Tube ◽  
Cancer Progression ◽  
Drug Targets ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Cell Of Origin ◽  
Pax8 Expression

High-grade serous ovarian cancer is a deadly disease that can originate from the fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2 and PAX8 are lineage-specific transcription factors required during development of the fallopian tube but not in the development of the ovary. PAX2 expression is lost early in serous cancer progression, while PAX8 is expressed ubiquitously. These proteins are implicated in migration, invasion, proliferation, cell survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8 represents a promising drug strategy that could inhibit these pro-tumorigenic effects. In this review, we examine the implications of PAX2 and PAX8 expression in the cell of origin of serous cancer and their potential efficacy as drug targets by summarizing their role in the molecular pathogenesis of ovarian cancer.

scholarly journals Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shuang Zhang ◽  
Igor Dolgalev ◽  
Tao Zhang ◽  
Hao Ran ◽  
Douglas A. Levine ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Fallopian Tube ◽  
Cell Types ◽  
Ovarian Surface Epithelium ◽  
Genetically Engineered ◽  
Surface Epithelium ◽  
High Grade ◽  
Cell Of Origin ◽  
Ovarian Surface ◽  
Serous Ovarian Carcinoma

AbstractThe cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) both considered candidates. Here, by using genetically engineered mouse models and organoids, we assessed the tumor-forming properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation and Tp53 mutation in Pax8 + FTE caused Serous Tubal Intraepithelial Carcinoma (STIC), which metastasized rapidly to the ovarian surface. These events were recapitulated by orthotopic injection of mutant FTE organoids. Engineering the same genetic lesions into Lgr5 + OSE or OSE-derived organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. FTE- and OSE-derived tumors had distinct transcriptomes, and comparative transcriptomics and genomics suggest that human HGSOC arises from both cell types. Finally, FTE- and OSE-derived organoids exhibited differential chemosensitivity. Our results comport with a dualistic origin for HGSOC and suggest that the cell-of-origin might influence therapeutic response.

scholarly journals Loss of LKB1 and PTEN tumor suppressor genes in the ovarian surface epithelium induces papillary serous ovarian cancer

2013 ◽  
Vol 35 (3) ◽  
pp. 546-553 ◽  
Author(s):  
Pradeep S. Tanwar ◽  
Gayatry Mohapatra ◽  
Sarah Chiang ◽  
David A. Engler ◽  
LiHua Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
Serous Ovarian Cancer ◽  
Suppressor Genes ◽  
Ovarian Surface

scholarly journals Both Fallopian Tube and Ovarian Surface Epithelium Can Act as Cell-of-Origin for High Grade Serous Ovarian Carcinoma

2018 ◽  
Author(s):  
Shuang Zhang ◽  
Tao Zhang ◽  
Igor Dolgalev ◽  
Hao Ran ◽  
Douglas A. Levine ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Fallopian Tube ◽  
Ovarian Surface Epithelium ◽  
Genetically Engineered ◽  
Differential Sensitivity ◽  
Surface Epithelium ◽  
High Grade ◽  
Cell Of Origin ◽  
Ovarian Surface ◽  
Serous Ovarian Carcinoma

ABSTRACTThe cell-of-origin of high grade serous ovarian carcinoma (HGSOC) remains controversial, with fallopian tube epithelium (FTE) and ovarian surface epithelium (OSE) each suggested as candidates. Here, by using genetically engineered mouse models and novel organoid systems, we assessed the tumor-forming capacity and properties of FTE and OSE harboring the same oncogenic abnormalities. Combined RB family inactivation (via T121 expression) and Tp53 mutation in Pax8+ FTE caused transformation to Serous Tubal Intraepithelial Carcinoma (STIC), which rapidly metastasized to the ovarian surface. This mouse model was recapitulated by FTE organoids, which, upon orthotopic injection, generated widely metastatic HGSOC. The same genetic lesions in Lgr5+ OSE cells or organoids also caused metastatic HGSOC, although with longer latency and lower penetrance. Comparative transcriptome analysis was consistent with different human HGSOCs arising from FTE and OSE. Furthermore, FTE- and OSE-derived organoids showed differential sensitivity to HGSOC chemotherapeutics. Our results comport with a dualistic origin for HGSOC and suggest the cell-of-origin could influence therapeutic response.SIGNIFICANCEThe cell-of-origin for high grade serous ovarian carcinoma (HGSOC) has been controversial. By generating novel GEMMs and organoid models with the same oncogenic defects, we demonstrate that HGSOC can originate from either fallopian tube epithelium (FTE) or ovarian surface epithelium (OSE). Importantly, FTE- and OSE-derived tumors differ significantly in biologic properties.

Spontaneous transformation of the ovarian surface epithelium and the biology of ovarian cancer

1995 ◽  
pp. 145-156 ◽  
Author(s):  
H. Salazar ◽  
A. K. Godwin ◽  
L. A. Getts ◽  
J. R. Testa ◽  
M. Daly ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
Spontaneous Transformation ◽  
Ovarian Surface

scholarly journals Prolactin signaling drives tumorigenesis in human high grade serous ovarian cancer cells and in a spontaneous fallopian tube derived model

2018 ◽  
Vol 433 ◽  
pp. 221-231 ◽  
Author(s):  
Subbulakshmi Karthikeyan ◽  
Angela Russo ◽  
Matthew Dean ◽  
Daniel D. Lantvit ◽  
Michael Endsley ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Fallopian Tube ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Prolactin Signaling
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