Several cancer cell lines and/or tissues express CD200 including ovarian, testicular, renal cell carcinoma, melanoma, malignant mesothelioma, neuroblastoma, chronic lymphocytic leukemia, prostate, breast, and colon cancers. A growing body of evidence indicates that the CD200/CD200R1 pathway is exploited by the cancer cells to initiate immune evasion and tumor progression in several human solid tumors, CLL, AML, and multiple myeloma (MM). Consistent with this, CD200 appears to be a prognostic factor in multiple myeloma and in acute myeloid leukemia. In addition, CD200 is co-expressed with surface markers of CSCs found on prostate (CD44+), breast (CD44+CD24?), colon cancer (CD133+), and glioblastoma (CD133). These studies suggest that CD200 serves as a putative marker of CSC populations. Expression of CD200 on CSCs together with its known capability to activate signaling pathways that ultimately result in immune evasion would significantly enhance tumor cell proliferation. Activation of sonic hedgehog (Shh and B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) signaling cascades is typically associated with a proliferative response, increased DNA repair mechanism, and self-renewal characteristics of CSCs. Little is known, however, regarding the relationship between CD200 expression, these markers and a proliferative phenotype. Moreover, while CD200-mediated signaling and its downstream effects on immune evading mechanisms have been studied, little is known regarding CD200's activation of proliferative signals. Although CD200 was originally known as 'pro-tumor' protein, this 'pro-tumor' effect of CD200/CD200R1 interaction was occasionally challenged. CD200 induction reduced tumor formation and lung cancer in a murine model of B16 melanoma cells. The role of CD200 especially in wild-type tumor situation might vary depending on tumor type and its microenvironment, and is thus occasionally debated.
Jung Y-S, Vermeer PD, Vermeer DW, et al. CD200 is related to cancer-stem-cell features and modulates response to chemoradiation in head and neck squamous cell carcinoma. Head & neck. 2015;37(3):327-335. doi:10.1002/hed.23608.