Breast Cancer Research and Treatment

, Volume 136, Issue 1, pp 117–127

Further evidence for a role of tumor CD200 expression in breast cancer metastasis: decreased metastasis in CD200R1KO mice or using CD200-silenced EMT6

  • Anna Podnos
  • David A. Clark
  • Nuray Erin
  • Kai Yu
  • Reginald M. Gorczynski
Preclinical study

DOI: 10.1007/s10549-012-2258-3

Cite this article as:
Podnos, A., Clark, D.A., Erin, N. et al. Breast Cancer Res Treat (2012) 136: 117. doi:10.1007/s10549-012-2258-3

Abstract

Previous studies reported that CD200 expression on cells of the transplantable EMT6 mouse breast cancer line was increased during growth in immunocompetent mice. Low levels of expression persisted in NOD-SCID.IL-2γr−/− mice or mice with generalized over-expression of a CD200 transgene (CD200tg mice), despite the faster tumor growth in both of these latter strains. We also showed that CD200 expression (by the host and/or tumor cells) led to increased seeding of tumor cells to DLN in immunocompromised (CD200tg or NOD-SCID.IL-2γr−/−) vs immunocompetent mice, using limiting dilution cloning of tumor cells from DLN (vs contralateral lymph nodes, CLN). Evidence for an important role for CD200 expression in this increased metastasis came from the observation that neutralization of CD200 by anti-CD200mAbs decreased tumor metastasis and increased levels of cytotoxic anti-tumor immune cells in DLN. In the current studies, we have extended these observations by exploring tumor growth/metastasis in CD200R1 KO mice in which we have previously shown, in a transplant model, that expression of CD200 fails to deliver an immunosuppressive signal. In addition, we have studied local and metastatic growth in healthy control mice of EMT6 tumor cells stably transduced with shRNA able to silence CD200 expression. In both scenarios, decreased metastasis was observed, with increased immunity to EMT6 detected by cytotoxicity assays. In addition, adoptive transfer of DLN to control mice attenuated EMT6 metastases implying a potential therapeutic benefit from neutralizing CD200 expression in breast cancer.

Keywords

Breast cancerMetastasisCD200shRNACD200R1KOImmunotherapy

Supplementary material

10549_2012_2258_MOESM1_ESM.doc (58 kb)
Supplementary material 1 (DOC 58 kb)

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Anna Podnos
    • 1
  • David A. Clark
    • 1
    • 2
    • 3
    • 4
  • Nuray Erin
    • 1
  • Kai Yu
    • 1
  • Reginald M. Gorczynski
    • 1
    • 3
    • 4
  1. 1.University Health Network, Toronto General HospitalTorontoCanada
  2. 2.Department of Medicine and Juravinski Cancer CentreMcMaster UniversityHamiltonUSA
  3. 3.Department of Immunology, Faculty of MedicineUniversity of TorontoTorontoCanada
  4. 4.Institute of Medical ScienceUniversity of TorontoTorontoCanada