Increased lung/liver metastasis of human breast cancer cells in NOD.SCIDIL2rγ-/- mice after treatment with soluble CD200Fc (TUM7P.922)

Abstract

Abstract CD200 overexpression increases metastasis of tumor cells to draining lymph nodes. Increased levels of a soluble form of CD200, sCD200, occur in serum of ~50% breast cancer patients, and an immunoadhesin, linking CD200 to an immunoglobulin Fc region (CD200Fc) increases metastasis in experimental models. We investigated whether CD200 levels were increased in human breast cancer cells in mice, and if overexpression of CD200 increased metastasis. NOD.SCIDIL2rγ-/- mice received 5x105 cells of different human breast cancer cell lines (MCF7; HTB19; MDA-MB-231) injected into the mammary fat pad. Groups of mice received ongoing infusion of human CD200Fc (20μg/mouse at 72hr intervals for 4 weeks). Tumors were resected at ~0.7cm3, and snap frozen for PCR analysis. Mice were monitored post resection, and sacrificed 2-3 months later. Lung and liver metastatic nodules were enumerated, and tissue snap frozen for PCR analysis. All tumors growing in NOD.SCIDIL2rγ-/- mice expressed CD200, though parent (in vitro) cell lines were uniformly negative. CD200Fc increased lung and liver metastasis of all breast cancer lines tested. Tumor metastasis was associated with changes in gene expression in tumor tissue, with significant alterations in genes encoding matrix metalloproteinases, and transcription factors modulating inflammation. Further changes in gene expression were attributed to the effect of CD200Fc infusion. Our data suggests increased soluble CD200 promotes human breast cancer metastasis.