Role of CD200 expression in regulation of metastasis of EMT6 tumor cells in mice.

Previous studies have confirmed that levels of CD200 expression on the cells of the transplantable EMT6 mouse breast cancer line are increased markedly during growth in immunocompetent mice, unlike the persistent low levels of expression observed in NOD-SCID.IL-2(γr-/-) mice or mice with generalized over-expression of a CD200 transgene (CD200(tg) mice). Faster tumor growth occurs in both of these latter mice, with decreased evidence for a host immune reaction in lymph nodes draining the tumor (DLN). We now report evidence for a role for CD200 expression (by the host and/or tumor cells) in increased seeding of tumor cells to DLN in immunocompromised (CD200(tg) or NOD-SCID.IL-2(γr-/-)) vs immunocompetent mice, by limiting dilution cloning of tumor cells from DLN (vs contralateral lymph nodes, CLN), using control and GFP-tagged EMT6 cells. Neutralization of expressed CD200 by anti-CD200mAbs decreased the tumor metastasis at the same time as increasing detection of cytotoxic anti-tumor immune cells in DLN. Infusion of either anti-CD4 to deplete T-effector cells, or anti-TGFβ antibody, increased metastasis to DLN, as did indeed the infusion of EMT6 cells selected for the loss of TGFβRII expression. It is concluded that the increased CD200 expression by breast cancer cells (and/or host tissue) may be an important variable involved in determining the risk of metastasis.