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


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.


CONCLUSIONS
MDSC accumulation is tumor burden-dependent, and tumor-derived factors such as uPA and its receptor uPAR play a role in their recruitment.
Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, PO Box 016960, R-138, Miami, FL 33101, USA.
Dan
D
Ilkovitch
Roberto
R
Carrio
Diana M
DM
Lopez
D000818:Animals; D018845:CD11 Antigens / Q000235:genetics; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood* / Q000235:genetics
D018845:CD11 Antigens; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator