uPA and uPA-receptor are involved in cancer-associated myeloid-derived suppressor cell accumulation
Dan Ilkovitch1, Roberto Carrio, Diana M Lopez
1Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, PO Box 016960, R-138, Miami, FL 33101, USA.
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.
Related Concept Videos
Abnormal Proliferation
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Differentiation of Common Myeloid Progenitor Cells
Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Induced Pluripotent Stem Cells
Somatic cells are...


