Melanoma cell expression of CD200 inhibits tumor formation and lung metastasis via inhibition of myeloid cell functions.
CD200 is a cell surface glycoprotein that functions through engaging CD200 receptor on cells of the myeloid lineage and inhibits their functions. Expression of CD200 has been implicated in a variety of human cancer cells including melanoma cells and has been thought to play a protumor role. To investigate the role of cancer cell expression of CD200 in tumor formation and metastasis, we generated CD200-positive and CD200-negative B16 melanoma cells. Subcutaneous injection of CD200-positive B16 melanoma cells inhibited tumor formation and growth in C57BL/6 mice but not in Rag1⁻/⁻C57BL/6 mice. However, i.v. injection of CD200-positive B16 melanoma cells dramatically inhibited tumor foci formation in the lungs of both C57BL/6 and Rag1⁻/⁻C57BL6 mice. Flow cytometry analysis revealed higher expression of CD200R in Gr1⁺ myeloid cells in the lung than in peripheral myeloid cells. Depletion of Gr1⁺ cells or stimulation of CD200R with an agonistic antibody in vivo dramatically inhibited tumor foci formation in the lungs. In addition, treatment with tumor antigen specific CD4 or CD8 T cells or their combination yielded a survival advantage for CD200 positive tumor bearing mice over mice bearing CD200-negative tumors. Taken together, we have revealed a novel role for CD200-CD200R interaction in inhibiting tumor formation and metastasis. Targeting CD200R may represent a novel approach for cancer immunotherapy.
Department of Pathology and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, United States of America.
Fatemeh
F
Talebian
Jin-Qing
JQ
Liu
Zhenzhen
Z
Liu
Mazin
M
Khattabi
Yukai
Y
He
Ramesh
R
Ganju
Xue-Feng
XF
Bai
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D045744:Cell Line, Tumor; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D022423:Myeloid Cells / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009369:Neoplasms / Q000473:pathology; D064446:Orexin Receptors; D011956:Receptors, Cell Surface
D015703:Antigens, CD; D000954:Antigens, Surface; C477337:CD200R1 protein, human; D064446:Orexin Receptors; D011956:Receptors, Cell Surface; C042739:antigens, CD200