Multiparity activates interferon pathways in peritoneal adipose tissue and decreases susceptibility to ovarian cancer metastasis in a murine allograft model

Cancer Lett. 2017 Dec 28:411:74-81. doi: 10.1016/j.canlet.2017.09.028. Epub 2017 Sep 28.

Abstract

Ovarian cancer is the fifth leading cause of cancer deaths in U.S. women and the deadliest gynecologic malignancy. This lethality is largely due to the fact that most cases are diagnosed at metastatic stages of the disease when the prognosis is poor. Epidemiologic studies consistently demonstrate that parous women have a reduced risk of developing ovarian cancer, with a greater number of births affording greater protection; however little is known about the impact of parity on ovarian cancer metastasis. Here we report that multiparous mice are less susceptible to ovarian cancer metastasis in an age-matched syngeneic murine allograft model. Interferon pathways were found to be upregulated in healthy adipose tissue of multiparous mice, suggesting a possible mechanism for the multiparous-related protective effect against metastasis. This protective effect was found to be lost with age. Based on this work, future studies exploring therapeutic strategies which harness the multiparity-associated protective effect demonstrated here are warranted.

Keywords: Adipose tissue; Interferons (IFNs); Murine age-matched model of parity; Ovarian cancer metastasis; Parity.

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / pathology
  • Allografts
  • Animals
  • Carcinoma, Ovarian Epithelial
  • Disease Models, Animal
  • Disease Susceptibility
  • Female
  • Interferons / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Parity*
  • Peritoneal Neoplasms / metabolism
  • Peritoneal Neoplasms / prevention & control
  • Peritoneal Neoplasms / secondary
  • Peritoneum / metabolism*
  • Peritoneum / pathology
  • Pregnancy
  • Risk Factors

Substances

  • Interferons