scholarly journals Expression of ovarian tumour suppressor OPCML in the female CD-1 mouse reproductive tract

Reproduction ◽  
2009 ◽  
Vol 137 (4) ◽  
pp. 721-726
Author(s):  
Jean S Fleming ◽  
H James McQuillan ◽  
Melanie J Millier ◽  
Grant C Sellar
Keyword(s):  
Reproductive Tract ◽  
Reproductive Function ◽  
Ovarian Surface Epithelium ◽  
Ovarian Tumour ◽  
Surface Epithelium ◽  
Cell Of Origin ◽  
Ductal Cells ◽  
Ovarian Cancers ◽  
Opioid Binding ◽  
Protein Cell

Opioid binding protein/cell adhesion molecule-like gene (OPCML) is frequently inactivated in epithelial ovarian cancer, but the role of this membrane protein in normal reproductive function is unclear. The ovarian surface epithelium (OSE) is thought to be the cell of origin of most epithelial ovarian cancers, some of which arise after transformation of OSE cells lining ovarian inclusion cysts, formed during ovulation. We used immunohistochemistry, immunoblotting and quantitative RT-PCR (qRT-PCR) to investigate OPCML expression in the uteri and ovaries of cycling 3-month CD-1 mice, as well as in ovaries from older mice containing inclusion cysts derived from rete ovarii tubules. Immunoblotting showed OPCML bands in uterine, but not whole ovarian or muscle extracts. Strong OPCML immunoreactivity was observed in oviduct, rete ovarii and uterus, whereas in ovary more immunoreactivity was seen in granulosa cells than OSE. No staining was observed in OSE around ovulation sites, where OSE cells divide to cover the site. OPCML immunoreactivity was also weaker in more dysplastic cells lining large ovarian inclusion cysts, compared with normal rete ovarii. No significant changes inOpcmlmRNA expression were observed in whole ovarian and uterine extracts at different stages of the cycle. We conclude that murine OPCML is more consistently expressed in cells lining the uterus, oviduct and rete ovarii than in ovary and is not expressed in OSE associated with ovulation sites. This observation supports the hypothesis that a proportion of epithelial ovarian cancers arise from ductal cells and other epithelia of the secondary Mullerian system, rather than the OSE.

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 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 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.

Potential role of gonadotrophin-releasing hormone (GnRH)-I and GnRH-II in the ovary and ovarian cancer.

2003 ◽  
pp. 169-177 ◽  
Author(s):  
S K Kang ◽  
K-C Choi ◽  
H-S Yang ◽  
P C K Leung
Keyword(s):  
Ovarian Cancer ◽  
Potential Role ◽  
Ovarian Surface Epithelium ◽  
Ovarian Tumour ◽  
Surface Epithelium ◽  
Releasing Hormone ◽  
Gnrh Receptors ◽  
Ovarian Cells ◽  
Gonadotrophin Releasing Hormone

Gonadotrophin-releasing hormone (GnRH) functions as a key neuroendocrine regulator of the hypothalamic-pituitary-gonadal axis. In addition to the hypothalamus and pituitary gland, GnRH and its receptor have been detected in other reproductive tissues including the gonads, placenta and tumours arising from these tissues. Recently, a second form of GnRH (GnRH-II) and type II GnRH receptor have been found in normal ovarian surface epithelium and neoplastic counterparts. The two types of GnRH may play an important role as an autocrine/paracrine regulator of reproductive functions and ovarian tumour growth. In this review, the distribution and potential roles of GnRH-I/-II and their GnRH receptors in the ovarian cells and ovarian cancer will be discussed.

The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms

2007 ◽  
Vol 9 (13) ◽  
pp. 1-12 ◽  
Author(s):  
Honami Naora
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Solid Tumours ◽  
Surface Epithelium ◽  
Cell Of Origin ◽  
Histopathological Features ◽  
Ovarian Cancers ◽  
Considerable Debate ◽  
Simple Surface

Epithelial ovarian cancer comprises several subtypes of tumours that exhibit diverse histopathological features. The intriguing assumption by many epithelial ovarian cancers of specialised features of nonovarian tissue lineages has promoted considerable debate as to whether these tumours arise from the deceptively simple surface epithelium of the ovary. This review focuses on recent molecular and pathological studies of epithelial ovarian cancers that support and challenge their surface-epithelial derivation, and discusses the findings in the context of current views of the ‘cell-of-origin’ of solid tumours.

scholarly journals Telomerase in the ovary

Reproduction ◽  
2010 ◽  
Vol 140 (2) ◽  
pp. 215-222 ◽  
Author(s):  
Jun-Ping Liu ◽  
He Li
Keyword(s):  
Ovarian Cancer ◽  
Germ Cells ◽  
Granulosa Cells ◽  
Reproductive Function ◽  
Ovarian Surface Epithelium ◽  
Malignant Cell ◽  
Telomerase Activity ◽  
Ovary Development ◽  
Surface Epithelium ◽  
Neoplastic Cells

Telomerase, an enzyme complex that binds the chromosome ends (telomeres) and maintains telomere length and integrity, is present in germ cells, proliferative granulosa cells, germline stem cells, and neoplastic cells in the ovary, but it is absent in differentiated or aged cells. Activation of telomerase in the ovary underpins both benign and malignant cell proliferation in several compartments, including the germ cells, membrana granulosa, and the ovarian surface epithelium. The difference in telomerase operation between normal and abnormal cell proliferations may lie in the mechanisms of telomerase activation in a deregulated manner. Recent studies have implicated telomerase activity in ovarian cancer as well as oogenesis and fertility. Inhibition of telomerase and the shortening of telomeres are seen in occult ovarian insufficiency. Studies of how telomerase operates and regulates ovary development may provide insight into the development of both germ cells for ovarian reproductive function and neoplastic cells in ovarian cancer. The current review summarizes the roles of telomerase in the development of oocytes and proliferation of granulosa cells during folliculogenesis and in the process of tumorigenesis. It also describes the regulation of telomerase by estrogen in the ovary.

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