Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation

• Main Authors: Tan, Kar Wai, Kato, Masashi, Keeble, Jo, Wang, Xiaojie, Hubert, Sandra, Barron, Luke, Tan, Nguan Soon, Angeli, Veronique, Abastado, Jean-Pierre, Tham, Muly, Prevost-Blondel, Armelle
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2015
• Subjects: DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/79494; http://hdl.handle.net/10220/24702; http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2482
• Institution: Nanyang Technological University

M2 macrophages promote tumor growth and metastasis, but their interactions with specific tumor cell populations are poorly characterized. Using a mouse model of spontaneous melanoma, we showed that CD34- but not CD34+ tumor-initiating cells (TICs) depend on M2 macrophages for survival and proliferation. Tumor-associated macrophages (TAMs) and macrophage-conditioned media protected CD34- TICs from chemotherapy in vitro. In vivo, while inhibition of CD115 suppressed the macrophage-dependent CD34- TIC population, chemotherapy accelerated its development. The ability of TICs to respond to TAMs was acquired during melanoma progression and immediately preceded a surge in metastatic outgrowth. TAM-derived transforming growth factor-β (TGFβ) and polyamines produced via the Arginase pathway were critical for stimulation of TICs and synergized to promote their growth.