Abstract 2887: Macrophage conditioned medium promotes colon cancer stem cell phenotype via the hedgehog signaling pathway

Background: Contradicting studies have shown that increased macrophages infiltration in colorectal cancer (CRC) could either result in anti-tumoral or in pro-tumoral effects. Because of these inconsistencies, we sought to determine the role of conditioned medium from macrophages, in particular classically activated macrophages, on the development of the CSC phenotype in CRC cells, which is believed to mediate tumor growth and chemoresistance. Methods: Murine (CT26) and human (HCP-1) CRC cell lines were treated with conditioned media (CM) from lipopolysaccharide (LPS)-activated murine macrophages. Viability studies were performed using the MTT assay, annexin V-FITC assay, and Western blot analysis. The CSC population was assessed using the sphere-forming assay and aldehyde dehydrogenase assay. Results: The results showed that 1) murine LPS-activated macrophage CM induced apoptosis in murine and human CRC cells, 2) murine and human LPS-activated macrophage CM secreted paracrine factors that promoted the CSC phenotype in murine and human CRC cells via the Sonic hedgehog (SHH)-Gli signaling pathway, which is known to drive self-renewal and 3) these effects were blocked by depletion of SHH in macrophage CM. Conclusions: Our data show that LPS-activated macrophages play an active role in promoting the CSC phenotype through activation of the SHH-Gli signaling pathway. Citation Format: Fan Fan, Rui Wang, Delphine R. Boulbes, Huiyuan Zhang, Stephanie S. Watowich, Rajat Bhattacharya, Ling Xia, Xiang-Cang Ye, Lee M. Ellis. Macrophage conditioned medium promotes colon cancer stem cell phenotype via the hedgehog signaling pathway [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 2887. doi:10.1158/1538-7445.AM2017-2887