uPA and uPA-receptor are involved in cancer-associated myeloid-derived suppressor cell accumulation

Anticancer Res. 2012 Oct;32(10):4263-70.

Abstract

Background: Myeloid-derived suppressor cells (MDSC) have been shown to play a critical role in tumor-induced immunosuppression, in many mouse and human cancers. The aim of this study was to show that MDSC accumulation is tumor burden-dependent, and to investigate the role of the tumor-derived urokinase plasminogen activator (uPA) and its receptor (uPAR) on MDSC recruitment.

Materials and methods: Levels of MDSC were assessed in tumor-bearers, and the ability to recruit MDSC by uPA was investigated in normal, tumor-bearers, uPAR(-/-), and CD11b(-/-) mice. uPAR expression in MDSC was also explored.

Results: MDSC accumulate to dramatic levels in tumor-bearers, and tumor-derived factors such as uPA also increase to great levels in circulation. MDSC can be recruited by uPA, and uPAR but not CD11b are required for such recruitment.

Conclusion: MDSC accumulation is tumor burden-dependent, and tumor-derived factors such as uPA and its receptor uPAR play a role in their recruitment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD11 Antigens / genetics
  • Carcinoma, Lewis Lung / genetics
  • Carcinoma, Lewis Lung / metabolism
  • Female
  • Gene Knockdown Techniques
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism*
  • Melanoma / genetics
  • Melanoma / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells / metabolism*
  • Receptors, Urokinase Plasminogen Activator / analysis
  • Receptors, Urokinase Plasminogen Activator / metabolism*
  • T-Lymphocytes, Regulatory / metabolism*
  • Tumor Burden
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / blood*
  • Urokinase-Type Plasminogen Activator / genetics

Substances

  • CD11 Antigens
  • Receptors, Urokinase Plasminogen Activator
  • Urokinase-Type Plasminogen Activator