Abstract PR11: Hematopoietic system aging has profound effects on the breast tumor microenvironment and cancer progression

Abstract

The majority of breast neoplasms are diagnosed in patients who are between the ages of 65 and 80. Although tumor growth is generally less aggressive and metastasis is less prevalent in older patients than in younger patients, elderly patients suffer the highest mortality and morbidity associated with breast cancer and breast cancer treatment. The reasons for age-dependent differences in incidence and aggressiveness of breast cancer are not understood. Treatment of breast cancer patients therefore presents age-specific challenges. We recently established mouse and human xenograft breast tumor models that mimic the age dependent disease progression that is observed in breast cancer patients, whereby tumor cells implanted into aged mice had lower incidence and slower growth kinetics than when implanted into young mice. Moreover, alpha-smooth muscle actin-positive myofibroblasts within the tumor microenvironment were significantly less prevalent in the tumors from aged mice than in size-matched tumors from young mice. We discovered that bone marrow derived cells from aged mice were significantly less effective in supporting breast cancer progression than the counterpart cells from young mice. Strikingly, bone marrow derived cells from young mice rescued tumor growth and stromal desmoplasia in aged mice. We are elucidating some of the molecular and phenotypic differences between young and aged tumor-promoting bone marrow cells. For example, we found that bone marrow cells from aged mice express lower levels of the cytokine, granulin, which is known to activate normal mammary fibroblasts in young mice. Our findings indicate that the age of the host hematopoietic system is a powerful determinant of breast tumor progression. Defining functional and molecular differences between tumor supportive hematopoietic cells in young and aged hosts should lay a foundation for further work in this relatively uncharted area of cancer research. Understanding tumor support mechanisms that exist in young and aged hosts should suggest new ideas for preclinical development of age-stratified breast cancer therapies. Citation Format: Timothy Marsh, Irene Wong, Amey Barakat, Yuanbo Qin, Sandra S. McAllister. Hematopoietic system aging has profound effects on the breast tumor microenvironment and cancer progression. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr PR11. doi:10.1158/1538-7445.CHTME14-PR11