TY - JOUR
T1 - Melanoma-initiating cells exploit M2 macrophage TGFβ and arginase pathway for survival and proliferation
AU - Tham, Muly
AU - Tan, Kar Wai
AU - Keeble, Jo
AU - Wang, Xiaojie
AU - Hubert, Sandra
AU - Barron, Luke
AU - Tan, Nguan Soon
AU - Kato, Masashi
AU - Prevost-Blondel, Armelle
AU - Angeli, Veronique
AU - Abastado, Jean Pierre
PY - 2014
Y1 - 2014
N2 - 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 macrophagedependent 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.
AB - 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 macrophagedependent 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.
KW - Arginase
KW - Macrophages
KW - TGFβ
KW - Tumor-initiating cell
UR - http://www.scopus.com/inward/record.url?scp=84920023709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84920023709&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.2482
DO - 10.18632/oncotarget.2482
M3 - Article
C2 - 25294815
AN - SCOPUS:84920023709
SN - 1949-2553
VL - 5
SP - 12027
EP - 12042
JO - Oncotarget
JF - Oncotarget
IS - 23
ER -