Melanoma cell expression of CD200 inhibits tumor formation and lung metastasis via inhibition of myeloid cell functions

• Published in: PloS one 2012-02, Vol.7 (2), p.e31442-e31442
• Main Authors: Talebian, Fatemeh, Liu, Jin-Qing, Liu, Zhenzhen, Khattabi, Mazin, He, Yukai, Ganju, Ramesh, Bai, Xue-Feng
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies; Antigens; Antigens, CD - biosynthesis; Antigens, Surface; Arthritis; B cells; Biology; Breast cancer; Cancer; Cancer immunotherapy; Cancer metastasis; Cancer therapies; Cancer treatment; CD200 antigen; CD4 antigen; CD4-Positive T-Lymphocytes; CD8 antigen; CD8-Positive T-Lymphocytes; Cell adhesion & migration; Cell Line, Tumor; Cell surface; Cell survival; Cytometry; Flow cytometry; Glycoproteins; Granulocytes; House mouse; Humans; Immunotherapy; Injection; Laboratory animals; Lung cancer; Lung Neoplasms - secondary; Lungs; Lymphocytes; Lymphocytes T; Lymphoma; Medicine; Melanoma; Melanoma - metabolism; Melanoma - pathology; Metastases; Metastasis; Mice; Myeloid cells; Myeloid Cells - pathology; Neoplasm Metastasis - prevention & control; Neoplasms - pathology; Ovarian cancer; Pathology; Phosphorylation; RAG1 protein; Receptors, Cell Surface; Rodents; Studies; T cells; Transgenic animals; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0031442

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.