Inflammation is a key contributor to ovarian cancer cell seeding

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.

<p>Ovarian cancer in the world: epidemiology and risk factors</p>

“…Ness et al,60 in a case-control study, supported the hypothesis that suggests inflammation contributes to the onset of ovarian cancer. On the other hand, Jia et al61 concluded that events associated with inflammation in the ovary (such as repairing the damaged ovary) are associated with an increase in the release of cancer cells in the tissues around the ovary. Thus, they stated that ovulation and other events associated with inflammation in the ovary contribute to an increased risk of ovarian cancer.…”

Factors in Oncogenesis: Viral Infections in Ovarian Cancer

“…In vivo stimulation of ovulatory wound repair, ovulation, and ovarian surface scarring increases the seeding of cancer cells and infiltration of immune cells at the wound site and tissues surrounding the ovary. Inflammatory events during ovulation and ovulatory wound repair contribute to an increased risk of OC [33].…”

The Ovarian Transcriptome of Reproductively Aged Multiparous Mice: Candidate Genes for Ovarian Cancer Protection

“…Mouse models have been used to study OC risk factors, including obesity [15], inflammation [16], age [8], and genetic inheritance [17], among others. Continuing the recent work on peritoneal tumor spread and systemic inflammation in an aged syngeneic female C57BL/6 mouse model of OC maintained in multiparous and nulliparous regimens [18], here, we studied the effect of parity history on the ovarian transcriptome in intact, uninduced animals.…”