Aging Increases Susceptibility to Ovarian Cancer Metastasis in Murine Allograft Models and Alters Immune Composition of Peritoneal Adipose Tissue

Abstract

Ovarian cancer, the most deadly gynecological malignancy in U.S. women, metastasizes uniquely, spreading through the peritoneal cavity and often generating widespread metastatic sites before diagnosis. The vast majority of ovarian cancer cases occur in women over 40 and the median age at diagnosis is 63. Additionally, elderly women receive poorer prognoses when diagnosed with ovarian cancer. Despite age being a significant risk factor for the development of this cancer, there are little published data which address the impact of aging on ovarian cancer metastasis. Here we report that the aged host is more susceptible to metastatic success using two murine syngeneic allograft models of ovarian cancer metastasis. This age-related increase in metastatic tumor burden corresponds with an increase in tumor infiltrating lymphocytes (TILs) in tumor-bearing mice and alteration of B cell-related pathways in gonadal adipose tissue. Based on this work, further studies elucidating the status of B cell TILs in mouse models of metastasis and human tumors in the context of aging are warranted.

With Great Age Comes Great Metastatic Ability: Ovarian Cancer and the Appeal of the Aging Peritoneal Microenvironment

“…In vivo models of intraperitoneal (IP) metastasis have been utilized to demonstrate an age-related difference in tumor burden in mice injected with ovarian tumor cells. When IP injected with syngeneic tumor cell lines, both C57Bl/6 and FVB mice exhibited a dramatic difference in disease progression between the young (3–6 months) and aged (20–23 months) cohort, with the aged mice harboring greater tumor burden than their younger counterparts [ 26 ]. Transcriptome analysis of gonadal adipose tissue from young and aged mice points to a difference in immune response in the aged mice but it is likely that the immune system is only one of the components of the microenvironment that is contributing to the age-related disparity in metastasis [ 26 ].…”

“…Interestingly, the role of p53 also varies greatly between OvCa cells and microenvironment. It was reported that in a C57Bl/6 model, ID8 cells with a p53 deletion showed greater tumor growth than the ID8 parental cells [ 26 ]. However, p53 is overexpressed in the aging OvCa tumor microenvironment as a result of oxidative stress, oncogenic stress and DNA damage [ 27 , 28 ].…”

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

“…Interestingly, in the ID8 allograft model, aged multiparous animals had no resilience to metastasis compared to their primiparous and nulliparous counterparts, suggesting one of the following: that the parity-related protective effect dwindles with age, that age-related effects override the parity-related protection against metastasis, or a combination of both. With this consideration, it is interesting to note that data from our laboratory demonstrate that aged mice are more susceptible to metastasis compared to young mice [48]. …”

The Response of Second Line Chemotherapy Platinum Resistant Ovarian Cancer in Sudan: 2013-2017

“…The lifetime risk of developing ovarian cancer in general population is 1.4 per cent and the mean age of presentation is 64 years, even though his incidence are varied by regions (7). Many factors play major role in the disease development and these includes advance age (8,9), genetics associations (10)(11)(12), early menstruation (13), late menopausal age (14) and hormonal therapy (15). An ovarian tumor mainly originates from its own tissue but some multiple tumors such as colon (16), stomach (17), small intestine (18), pancreas (6), breast (19) and even thyroid cancer (20) can be metastasis to the ovary.…”