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

Fatemeh Talebian, Jin Qing Liu, Zhenzhen Liu, Mazin Khattabi, Yukai He, Ramesh Ganju, Xue Feng Bai

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere31442
JournalPloS one
Volume7
Issue number2
DOIs
StatePublished - Feb 3 2012

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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