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

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.

• Authors: Dan Ilkovitch, Roberto Carrio, Diana M Lopez
• Journal: Anticancer research (Anticancer Res) Vol. 32 Issue 10 Pg. 4263-70 (Oct 2012) ISSN: 1791-7530 [Electronic] Greece
• PMID: 23060546 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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