Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

Although stromal cell signaling has been shown to play a significant role in the progression of many cancers, relatively little is known about its importance in modulating ovarian cancer development. The purpose of this study was to investigate the process of stroma activation in human ovarian cancer by molecular analysis of matched sets of cancer and surrounding stroma tissues. RNA microarray profiling of 45 tissue samples was carried out using the Affymetrix (U133 Plus 2.0) gene expression platform. Laser capture microdissection (LCM) was employed to isolate cancer cells from the tumors of ovarian cancer patients (Cepi) and matched sets of surrounding cancer stroma (CS). For controls, ovarian surface epithelial cells (OSE) were isolated from the normal (noncancerous) ovaries and normal stroma (NS). Hierarchical clustering of the microarray data resulted in clear separations between the OSE, Cepi, NS, and CS samples. Expression patterns of genes encoding signaling molecules and compatible receptors in the CS and Cepi samples indicate the existence of two subgroups of cancer stroma (CS) with different propensities to support tumor growth. Our results indicate that functionally significant variability exists among ovarian cancer patients in the ability of the microenvironment to modulate cancer development.

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Targeting progesterone signaling prevents metastatic ovarian cancer

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2013595117 ◽

2020 ◽

Vol 117 (50) ◽

pp. 31993-32004

Author(s):

Olga Kim ◽

Eun Young Park ◽

Sun Young Kwon ◽

Sojin Shin ◽

Robert E. Emerson ◽

...

Keyword(s):

Ovarian Cancer ◽

Deleterious Mutation ◽

Peritoneal Metastases ◽

Cancer Development ◽

Serous Carcinoma ◽

Cancer Type ◽

High Grade ◽

Primary Tumors ◽

High Risk Populations ◽

Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

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CEMIP promotes ovarian cancer development and progression via the PI3K/AKT signaling pathway

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2019.108787 ◽

2019 ◽

Vol 114 ◽

pp. 108787 ◽

Cited By ~ 8

Author(s):

Fan Shen ◽

Zhi-hong Zong ◽

Yao Liu ◽

Shuo Chen ◽

Xiu-jie Sheng ◽

...

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Akt Signaling ◽

Cancer Development ◽

Akt Signaling Pathway

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Mechanisms of Cables 1 gene inactivation in human ovarian cancer development

Cancer Biology & Therapy ◽

10.4161/cbt.7.2.5253 ◽

2008 ◽

Vol 7 (2) ◽

pp. 180-188 ◽

Cited By ~ 13

Author(s):

Hideo Sakamoto ◽

Anne M. Friel ◽

Antony W. Wood ◽

Lankai Guo ◽

Ana Ilic ◽

...

Keyword(s):

Ovarian Cancer ◽

Gene Inactivation ◽

Cancer Development ◽

Human Ovarian Cancer

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Gene therapy for ovarian cancer: development of novel treatment strategies

International Journal of Gynecological Cancer ◽

10.1046/j.1525-1438.1997.00411.x ◽

1997 ◽

Vol 7 (1) ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

O. Dorigo ◽

J. S. Berek

Keyword(s):

Ovarian Cancer ◽

Gene Therapy ◽

Treatment Strategies ◽

Cancer Development ◽

Novel Treatment ◽

Novel Treatment Strategies

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Endometriosis and endometriosis-associated cancers: new insights into the molecular mechanisms of ovarian cancer development

ecancermedicalscience ◽

10.3332/ecancer.2018.803 ◽

2018 ◽

Vol 12 ◽

Cited By ~ 23

Author(s):

Amy Dawson ◽

Marta Llauradó Fernandez ◽

Michael Anglesio ◽

Paul J Yong ◽

Mark S Carey

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanisms ◽

Cancer Development

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Dynamic changes in the urine proteome in two ovarian cancer rat models

10.1101/604850 ◽

2019 ◽

Author(s):

Yuqiu Li ◽

Linpei Zhang ◽

Wenshu Meng ◽

Youhe Gao

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Cancer Progression ◽

The Body ◽

Cancer Development ◽

Ovarian Cancer Cells ◽

Rat Models ◽

Gynecological Malignancy ◽

Injection Model ◽

Differential Proteins

AbstractOvarian cancer is the most lethal gynecological malignancy in women, and it is likely to metastasize and has a poor prognosis. The early and reliable diagnosis and monitoring of ovarian cancer is very important. Without a homeostasis mechanism, urine can reflect early systemic changes in the body and has a great potential to be used for the early detection of cancer. This study tested whether early changes could be detected in two ovarian cancer rat models. Two rat models were established by either intraperitoneal (i.p.) or orthotopic (o.t.) injection of NuTu-19 ovarian cancer cells in female Fischer344 rats. Urine samples from ovarian cancer rats were collected at five time points during cancer development, and urinary proteins from the rats were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Compared with pre-injection samples, 49 differential proteins that have human orthologues were significantly changed in the orthotopically injected model. Among them, 24 of the differential proteins have previously been reported to be associated with ovarian cancer, six of which were reported to be biomarkers of ovarian cancer. On the 7th day after orthotopic injection, four differential proteins (APOA1, OX2G, CHMP5, HEXB) were identified before obvious metastases appeared. In the intraperitoneal injection model, 76 differential proteins were changed during the course of ovarian cancer development. The results show that urine proteins could enable the early detection and monitoring of ovarian cancer progression and could lay a foundation for further exploration of the biomarkers of ovarian cancer.

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