黑色素瘤起始细胞利用M2巨噬细胞的转化生长因子β和精氨酸酶途径来实现存活和增殖。
Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation.
作者信息
Tham Muly, Tan Kar Wai, Keeble Jo, Wang Xiaojie, Hubert Sandra, Barron Luke, Tan Nguan Soon, Kato Masashi, Prevost-Blondel Armelle, Angeli Veronique, Abastado Jean-Pierre
机构信息
Singapore Immunology Network, BMSI, A-STAR, Singapore.
Singapore Immunology Network, BMSI, A-STAR, Singapore. Department of Clinical Research, Singapore General Hospital, Singapore.
出版信息
Oncotarget. 2014 Dec 15;5(23):12027-42. doi: 10.18632/oncotarget.2482.
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.
M2巨噬细胞促进肿瘤生长和转移，但其与特定肿瘤细胞群体的相互作用却鲜有描述。利用自发黑色素瘤小鼠模型，我们发现CD34⁻而非CD34⁺肿瘤起始细胞（TICs）的存活和增殖依赖于M2巨噬细胞。肿瘤相关巨噬细胞（TAMs）和巨噬细胞条件培养基在体外可保护CD34⁻ TICs免受化疗影响。在体内，抑制CD115可抑制巨噬细胞依赖的CD34⁻ TIC群体，而化疗则加速其发展。TICs对TAMs作出反应的能力是在黑色素瘤进展过程中获得的，且紧接转移灶大量出现之前。TAM衍生的转化生长因子-β（TGFβ）和通过精氨酸酶途径产生的多胺对TICs的刺激至关重要，并协同促进其生长。
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