Abstract
The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. Most ovarian cancers originate in the fallopian tube with subsequent implantation of malignant cells into the ovary. However, the events and conditions that lead to cancer cell implantation are unknown. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. We found that the dominant site of cancer cell seeding was not the ovary but the nearby surgical wound site, which was associated with a strong and persistent inflammatory reaction. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. Changes in the ovary not accompanied by inflammation, such as completed ovulatory cycles and fully-healed scars on the ovarian surface, did not contribute to increased cancer cell seeding. We conclude that inflammation is the most likely mechanism by which ovulation and postmenopausal events contribute to the increased risk of ovarian cancer.
Highlights
The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear
To simulate cancer cell seeding and entrapment during ovulatory wound healing, superovulation was induced in 4 week-old female FVB mice by intraperitoneal injection of pregnant mare serum (PMS) and human chorionic gonadotropin (hCG) hormones or phosphate buffered saline (PBS)
Most early stage cancers in the tubal fimbria are associated with a dominant mass in the ovary, indicating that the ovarian microenvironment is essential for tumor growth
Summary
The incidence of ovarian cancer dramatically increases in early menopause but the factors contributing to cancer onset are unclear. To quantify which conditions are conducive to the seeding of cancer cells in an immunocompetent mouse model, we surgically implanted mouse ovarian cancer cells into the oviducts of syngeneic mice and simulated conditions associated with ovulatory wound repair, incessant ovulation, ovarian surface scarring, and aging. Conditions in the ovary associated with inflammation, such as acute ovulatory wound repair, active healing of the scarred ovarian surface, and mouse aging, contributed to increased seeding of the cancer cells to the surgical wound site and tissues surrounding the ovary. We used a mouse model to study events associated with ovulation and ovulatory wound repair, including epithelial cell entrapment and the formation of epithelial inclusion cysts[18] We extended those studies by simulating various postmenopausal conditions in mice and quantifying cancer cell deposits for each condition. Our data show that premenopausal and postmenopausal conditions contribute to increased cancer cell seeding only in the presence of an inflammatory reaction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
