Abstract TMEM-029: AGING INCREASES SUSCEPTIBILITY TO OVARIAN CANCER METASTASIS IN A MURINE ALLOGRAFT MODEL

Abstract

Abstract Ovarian cancer (OvCa) is the leading gynecological malignancy in women in the United States. OvCa metastasizes uniquely, spreading through the peritoneal cavity and generating widespread metastatic sites. The vast majority of OvCa cases occur in women over 40 and the median age at diagnosis is 63 (SEER). Despite age being a significant risk factor for the development of OvCa, there is a paucity of studies addressing the role of aging in OvCa metastasis. To our knowledge, there are no reports utilizing old mice to investigate the effects of age on metastasis in vivo. We designed a study using a C57BL/6 model of aging where young (Y) mice are 3-6 months of age and aged (A) mice are 20-23 months of age, corresponding to young (20-30 years) and aged (60-67 years) humans. Using the C57BL/6 syngeneic ID8 mouse ovarian surface epithelial cell line, we tested the effect of aging on metastatic success in vivo. An allograft study was carried out with Y and A mice that were intraperitoneally injected with 3.7x106 ID8 RFP-tagged cells. The mice were imaged once a week starting at 4.5 weeks post injection and were sacrificed for dissection at 8 weeks post injection. Live imaging suggested OvCa metastasis was more efficient in the aged animals than in the young animals. After dissection, the abdominal organs were imaged ex vivo and tumor burden was quantified. The aged mice displayed heavier tumor burden in the gonadal fat compared to the young. Interestingly, no difference in metastasis to the omentum was detected. To investigate why gonadal fat is more receptive to metastasis in the aged animals, periovarian adipose from 4 young and 4 aged healthy non-tumor bearing mice was isolated for RNAseq analysis. Several immune pathways involving B cells were found to be significantly upregulated in the RNA from aged animals. Studies will be conducted to elucidate the status of B cells in aging periovarian adipose, including immunohistochemistry for CD45 and other B cell markers upregulated in the RNAseq dataset. Citation Format: Elizabeth Loughran, Annemarie Leonard, Ryan Phan, Laura Tarwater, Tyvette Hilliard, Marwa Asem, Yueying Liu, Jing Yang, Yuliya Klymenko, Jeff Johnson, Zonggao Shi, Matthew Leevy, Matthew Ravosa and M. Sharon Stack. AGING INCREASES SUSCEPTIBILITY TO OVARIAN CANCER METASTASIS IN A MURINE ALLOGRAFT MODEL [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr TMEM-029.