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The immunosuppressive surface ligand CD200 augments the metastatic capacity of squamous cell carcinoma

Magda Stumpfova1, Desirée Ratner, Edward B Desciak

  • 1Departments of Pathology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.

Cancer Research
|March 25, 2010
PubMed

Insights

CD200 expression is low in primary skin cancer but high in metastases. This protein helps squamous cell carcinoma (SCC) cells survive by interacting with immune cells, promoting cancer spread.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • CD200 (OX-2) is a cell surface glycoprotein that suppresses immune responses via its receptor, CD200R, on myeloid cells.
  • CD200 signaling is crucial for tissue homeostasis but can also aid neoplastic cell survival.

Purpose of the Study:

  • To investigate the role of CD200 in squamous cell carcinoma (SCC) metastasis.
  • To determine how CD200 expression in SCC cells affects their interaction with the tumor microenvironment and metastatic potential.

Main Methods:

  • Analysis of CD200 expression in primary and metastatic SCC tissues.
  • Assessment of SCC cell proliferation, invasion, and tumor reconstitution in vivo.
  • Evaluation of the impact of CD200 expression on SCC cell metastasis and secondary tumor formation.
  • Characterization of CD200R-expressing stromal cells and their cytokine production.

Main Results:

  • CD200 expression is low in primary skin SCC but significantly induced in metastases.
  • Loss of CD200 impairs SCC metastasis, suggesting CD200(+) SCC cells rely on CD200R(+) immune cells for survival.
  • CD200R(+) cells in the tumor stroma are predominantly myeloid-derived suppressor cells (MDSCs).
  • MDSCs in the presence of SCC cells release elevated granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in a CD200-dependent manner.

Conclusions:

  • CD200 is a hallmark of SCC metastasis.
  • The interaction between CD200(+) SCC keratinocytes and CD200R(+) MDSCs is essential for metastatic survival.
  • Targeting the CD200-CD200R pathway may offer therapeutic strategies for SCC metastasis.

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