Rapid-fire talks

Saturday May 25, 2024 from 11:30 to 12:00

Room: Imperial

> Rapid-fire 11 (POS-44) Menopause induced senescence: a potential driver for ovarian cancer metastasis

Nhung Vuong-Robillard

Postdoctoral Fellow
Le Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM)

Abstract

Menopause induced senescence: a potential driver for ovarian cancer metastasis

Nhung Vuong-Robillard1,2, Kim Leclerc-Desaulniers1,2, Genève Perron-Deshaies1,2, Wenying Piao1,2, Gerardo Ferbeyre1,2, Anne-Marie Mes-Masson1,2.

1Centre de Recherche du Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada; 2Institut du Cancer de Montréal, Montreal, QC, Canada

Introduction: Epidemiology has observed an inverse correlation between frailty and age of menopause, while women undergoing prophylactic oophorectomy show signs of accelerated aging with a higher risk of multimorbidity. At the cellular level, we know that the accumulation of senescent (aged) cells impairs tissue regeneration and their chronic secretion of proinflammatory mediators is also tissue damaging. Since both natural and surgical menopause results in estrogen depletion, we hypothesize that prolonged estrogen loss following menopause accelerates senescent cell accumulation, and this sets the stage for inflammation driven diseases such as cancer.

Methods: The ovariectomy (OVX) mouse model of menopause was utilized to test our hypothesis where OVX and age matched mouse tissues were assessed for senescence markers. To follow up and establish the role senescent cells play in postmenopausal pathologies, senescence cells were eliminated by treating mice with senolytic drugs.

Results: OVX causes inflammation and senescent cell accumulation across many tissues but is most notable in the visceral adipose. Here, we discovered that both adipocytes and macrophages contribute to the senescent cell burden, and that senolytic treatment limited their accumulation in addition to preventing common phenotypes in postmenopausal women such as weight gain, inflammation, and early signs of metabolic dysfunction.

Conclusions: Our results show that OVX can accelerate both adipose and immune cell aging. This has implications for the role of senolytics in ovarian cancer treatment as ovarian cancer preferentially metastasizes to the visceral fat – the same tissue most affected by menopause induced senescence. Work is currently underway to determine if the presence of proinflammatory senescent cells primes the visceral adipose tissue contributes to cancer spread, and if senolytic therapy can limit adipose tissue colonization to improve patient outcomes.

Cancer Research Society Connie Lynn and Kenneth George Fenney Fund. Canadian Institutes of Health Research.

Presentations by Nhung Vuong-Robillard

© 2024 CCOCR 2024