Abstract 2954: The role of hedgehog signaling in breast cancer progression through macrophage polarization

Abstract

Abstract The tumor microenvironment is comprised of stromal cells that constantly crosstalk with the cancer cells. Stromal cells, specifically tumor infiltrating immune cells, secrete cytokines and chemokines that regulate host responses to cancer through tumor-suppressing or tumor-promoting mechanisms. Macrophages within the tumor microenvironment are very plastic and can modulate different functions that promote tumor growth or tumor suppression, depending on their phenotype. Classically activated macrophages (M1) suppress tumor growth by mounting a pro-inflammatory immune response; while alternatively activated macrophages (M2) promote tumor progression by inducing an anti-inflammatory response which suppresses immune system function. Hedgehog (Hh) signaling is essential for normal mammalian embryonic development by modulating vital functions such as cell proliferation, differentiation, and angiogenesis. Although the Hh signaling pathway is tightly controlled, it often is deregulated, thus promoting tumorigenesis and tumor progression. Aberrant Hh signaling has particularly been implicated in breast cancer progression and metastasis. In this project, we investigate the role of Hh signaling in polarizing cancer associated macrophages toward the tumor-promoting M2 phenotype in a breast cancer model. We have discovered that using small molecule inhibitors to inhibit Hh signaling attenuates the cytokine profile associated with M2 macrophages, while adding recombinant Hh ligand potentiates it. Our data thus far supports a role for Hh signaling in alternatively polarizing macrophages. We hypothesize that Hh inhibitors will reduce the abundance of M2 macrophages and prevent metastasis. Citation Format: Ann Hanna, Lalita A. Shevde. The role of hedgehog signaling in breast cancer progression through macrophage polarization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2954. doi:10.1158/1538-7445.AM2017-2954