Ovulation and extra-ovarian origin of ovarian cancer

Yang Yang‐Hartwich, Yang Yang-Hartwich, Marta Gurrea-Soteras, Natalia Sumi, Natália J. Sumi, Won Duk Joo, Jennie C Holmberg, Vinicius Craveiro, Ayesha B Alvero, Gil Mor
Scientific reports · 2014 · vol. 4(1) , pp. 6116 · doi:10.1038/srep06116 · PMID:25135607 · PMC4137344 · W2039313209
article OA: gold CC0 ⤵ 6 in-corpus citations
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Abstract

The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies.

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endometriosis

MeSH descriptors

Carcinoma Ovarian Neoplasms Animals Carcinoma Carcinoma Cell Line, Tumor Cell Movement Cell Movement Cell Transformation, Neoplastic Chemokine CXCL12 Chemokine CXCL12 Disease Models, Animal Female Humans Mice Mice, Nude Neoplastic Stem Cells Neoplastic Stem Cells Neoplastic Stem Cells Ovarian Neoplasms

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