Abstract 5117: A murine hematogenous bone metastatic cancer to model spontaneous metastasis of triple negative breast cancer

Abstract

Abstract The development of bone metastasis in breast cancer and its pathologic progression are known to be clinically important problem. It is known that immunologic response in microenvironment is important as soil in the bone metastasis process and progression. Thus, immunologic modulation is expected to play a role in the prevention and treatment of the disease in bone metastasis. However, most studies to date; researches in bone metastasis were carried out using human breast cancer cell lines in xenograft model of immuno-deficient mouse or in vitro co-culture system. These approaches have limitations in regard to interaction among immune cells, cancer cells, and other stroma cells. To overcoming these limitation, we used the C3(1)Tag mouse model to establish a spontaneous bone metastasis model. First, a cell line (M6) obtained from a spontaneously occurring tumor in C3(1)Tag mice was infected with lentiviral-luciferase. M6 cells with lentiviral-luciferase were administered using intracardiac injection and C3(1) Tag mice were monitored until tumors are detected under bioluminescence imaging. In 3 weeks, metastatic bone lesions were apparent in 85.7% of mice. To understand biologic characteristics of in vivo selected bone metastatic subpopulation, metastatic cancer cells were harvested and were analyzed using immunohistochemical staing in comparison with parent cells. Tumor cells metastasized to bone showed differential expression in HIF1A, c-MET, and EMT markers. Unexpectedly, bone metastatic cancers showed better sensitivity to paclitaxel and cisplatin than parent cells in cell viability assay. In addition, immune microenvironment in bone metastatic foci was assessed using multiplex immunohistochemical staining and showed an immune suppressive MDSCs infiltration. Taken together, we established a murine hematogenous bone metastatic cancer and characterized biologic characteristics to model human triple negative breast cancer. The potential targets identified in this study might be a future immunologic target in patients with bone metastasis. Citation Format: Hye Jin Lee. A murine hematogenous bone metastatic cancer to model spontaneous metastasis of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5117.