Abstract A42: The role of M1 and M2 macrophage in the cycling phase of breast cancer

Abstract

Abstract Breast cancer malignancy is the second leading cause of death among women. The majority of deaths associated with cancer, from solid tumors are the result of metastasis and not from the primary tumor site Clinical evidence indicates that breast cancer (BC) cells (BCC) can exist in dormancy within the bone marrow (BM), for >10 years. Methods by which BCCs adapt dormancy as well as reversed dormancy into metastatic cells are highly significant for the development of new and safe therapies. This research focuses on the BM because it is the preferred organ for dormant BCCs. Furthermore, in several cases, the BM has been identified as a source of BCCs during clinical resurgence. A subset of BCCs with tumor initiating property (cancer stem cells, CSCs) has been identified as those responsible for dormancy and chemoresistance. We will take advantage of our working hierarchy of BCCs to determine how M2 macrophage (MΦ) facilitates dormancy or clinical resurgence into metastatic cells. The mechanisms by which dormancy occurs followed by later resurgence into metastatic role for the BM microenvironment to facilitate CSC dormancy. CSCs can form gap junctional intercellular communication (GJIC) with stroma, by release of miRNA, which induces cycling quiescence. MΦ are classified into two subsets, either M1 or M2 type. M1 are mostly pro-inflammatory (classically activated to kill microorganisms and tumor cells), while M2 are non-inflammatory (alternatively activated to promote tissue repair). M2 MΦ is one cell type that comprises the stromal compartment inside the BM hematopoietic microenvironment. We studied how activated MSCs can influence M1 or M2 polarization. Our supporting studies indicate that M2 MΦ can arrest BCCs in G1/G0, while M1 MΦ can induce cell cycle progression. Activated MSCs transitioned M2 into M1 phenotype whereas inactivated MSCs maintains M2 MΦ phenotype. Here we present how the transitional changes in M2 to M1 MΦ affect the behavior of the CSCs within the BM stromal compartment. Citation Format: Nykia D. Walker, Michael Elias, Steve Greco, Pranela Rameshwar. The role of M1 and M2 macrophage in the cycling phase of breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A42.