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

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.

• Authors: Muly Tham, Kar Wai Tan, Jo Keeble, Xiaojie Wang, Sandra Hubert, Luke Barron, Nguan Soon Tan, Masashi Kato, Armelle Prevost-Blondel, Veronique Angeli, Jean-Pierre Abastado
• Journal: Oncotarget (Oncotarget) Vol. 5 Issue 23 Pg. 12027-42 (Dec 15 2014) ISSN: 1949-2553 [Electronic] United States
• PMID: 25294815 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Transforming Growth Factor beta
• Arginase

Topics

• Animals
• Arginase (metabolism)
• Cell Proliferation (physiology)
• Cell Survival (physiology)
• Disease Models, Animal
• Female
• Macrophages (immunology)
• Male
• Melanoma (immunology, metabolism, pathology)
• Mice
• Mice, Mutant Strains
• Neoplastic Stem Cells (immunology, metabolism, pathology)
• Signal Transduction (immunology)
• Transforming Growth Factor beta (metabolism)