Breast Cancer Research and Treatment

, Volume 130, Issue 1, pp 49–60

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

Authors

    • University Health Network, Toronto General Hospital
  • David A. Clark
    • University Health Network, Toronto General Hospital
    • Department Medicine and Juravinski Cancer CenterMcMaster University
  • Nuray Erin
    • School of Medicine, Department of Clinical PharmacologyAkdeniz University
  • Ismat Khatri
    • University Health Network, Toronto General Hospital
Preclinical study

DOI: 10.1007/s10549-010-1259-3

Cite this article as:
Gorczynski, R.M., Clark, D.A., Erin, N. et al. Breast Cancer Res Treat (2011) 130: 49. doi:10.1007/s10549-010-1259-3

Abstract

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-2γr−/− mice or mice with generalized over-expression of a CD200 transgene (CD200tg 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 (CD200tg or NOD-SCID.IL-2γr−/−) 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.

Keywords

Breast cancerMetastasisCD200 transgeneImmunotherapy

Supplementary material

10549_2010_1259_MOESM1_ESM.ppt (266 kb)
Supplementary material 1 (PPT 266 kb)
10549_2010_1259_MOESM2_ESM.docx (11 kb)
Supplementary material 2 (DOCX 11 kb)

Copyright information

© Springer Science+Business Media, LLC. 2010