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

Citations Over TimeTop 15% of 2014 papers

Abstract

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.

Related Papers

• → Differential regulation of arginases and inducible nitric oxide synthase in murine macrophage cells(1998)250 cited
• → Generation of a Mouse Model for Arginase II Deficiency by Targeted Disruption of the Arginase II Gene(2001)144 cited
• → Arginase I expression is upregulated by dietary restriction in the liver of mice as a function of age(2015)11 cited
• → Relationship between Arginase Activity and Nitric Oxide Production(2000)17 cited
• Beneficial Effect of Arginase A1 on Murine Septic Shock(2004)