title: 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.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore.
authors.forename: Muly
authors.initials: M
authors.lastname: Tham
authors.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore. Department of Clinical Research, Singapore General Hospital, Singapore.
authors.forename: Kar Wai
authors.initials: KW
authors.lastname: Tan
authors.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore.
authors.forename: Jo
authors.initials: J
authors.lastname: Keeble
authors.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Wang
authors.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore.
authors.forename: Sandra
authors.initials: S
authors.lastname: Hubert
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Luke
authors.initials: L
authors.lastname: Barron
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Nguan Soon
authors.initials: NS
authors.lastname: Tan
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.affiliation: Institut Cochin, Université Paris Descartes, CNRS UMR, Paris, France.
authors.forename: Armelle
authors.initials: A
authors.lastname: Prevost-Blondel
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Veronique
authors.initials: V
authors.lastname: Angeli
authors.affiliation: Singapore Immunology Network, BMSI, A-STAR, Singapore. Institut de Recherche Internationales Servier, 50 rue Carnot, Suresnes cedex, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008817:Mice, Mutant Strains; D014411:Neoplastic Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D016212:Transforming Growth Factor beta; D001119:Arginase