CCL2/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers.
In addition to direct effect on tumor cells, the tumor-promoting activity of CCL2 has been ascribed to its role in chemoattracting tumor-associated macrophages. However it is unclear whether CCL2 also attracts other immune regulatory cells during tumor development. In this study, we confirmed the ubiquitous expression of CCR2 in myeloid suppressor cells (MSCs), a main inducer for tumor immune evasion, and identified that cancer patient-derived CCL2 mediated the migration of MSCs to tumors in vitro, which could be interdicted by antibodies neutralizing CCL2 or blocking CCR2. In mouse tumor model, the adoptively transferred CCR2(-/-) MSCs could not migrate to either tumor or spleen as efficiently as WT MSCs. The absence of CCL2/CCR2 signaling hindered both MSC migration and MSC-promoted tumor growth. Our data provide evidence that CCL2/CCR2 pathway plays a pivotal role in MSC migration, which is a novel mechanism through which CCL2 promotes tumor growth.
Huang
Bo
B
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Lei
Zhang
Z
Zhao
Jie
J
Gong
Wei
W
Liu
Jinwen
J
Chen
Zhenyong
Z
Liu
Yi
Y
Li
Dong
D
Yuan
Ye
Y
Zhang
Gui-Mei
GM
Feng
Zuo-Hua
ZH
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D022423:Myeloid Cells / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D019138:Antibodies, Blocking; C515334:CCR2 protein, human; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2; D019707:Receptors, Chemokine