Activation of Urokinase Plasminogen Activator and Its Receptor Axis Is Essential for Macrophage Infiltration in a Prostate Cancer Mouse Model
Copyright policy )Activation of Urokinase Plasminogen Activator and Its Receptor Axis Is Essential for Macrophage Infiltration in a Prostate Cancer Mouse Model
Macrophages within the tumor microenvironment promote angiogenesis, extracellular matrix breakdown, and tumor cell migration, invasion, and metastasis. Activation of the urokinase plasminogen activator (uPA) and its receptor (uPAR) axis promotes prostate cancer tumorigenicity, invasion, metastasis, and survival within the tumor microenvironment. The link between macrophage infiltration and the uPA/uPAR axis in prostate cancer development has not been established, although it has been reported that uPA plays a critical role inmonocyte and macrophage chemotaxis. In this study, murine prostate cancer RM-1 cells were subcutaneously inoculated into wild-type (WT), uPA(-/-), and uPAR(-/-) mice. Tumor volume was significantly diminished in both uPA(-/-) and uPAR(-/-) mice compared with WT controls. Greater inhibition of tumor volume was also observed in uPA(-/-) mice compared with uPAR(-/-) mice, suggesting the important contribution of stromal-derived uPA to sustain the tumor growth. Immunohistochemical staining revealed that tumors in uPA(-/-) and uPAR(-/-) mice displayed significantly lower proliferative indices, higher apoptotic indices, and less neovascularity compared with the tumors in WT mice. Tumors in uPA(-/-) and uPAR(-/-) mice displayed significantly less macrophage infiltration as demonstrated by F4/80 staining and MAC3(+) cell numbers by flow cytometry compared with the tumors from WT mice. These findings suggest that the uPA/uPAR axis acts in both autocrine and paracrine manners in the tumor microenvironment, and activation of uPA/uPAR axis is essential for macrophage infiltration into prostate tumors.
- University of Michigan–Flint United States
- UNIVERSITY OF MICHIGAN AT ANN ARBOR
- University of Michigan–Ann Arbor United States
- U-M Rogel Cancer Center United States
Male, Mice, Knockout, Neovascularization, Pathologic, Macrophages, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prostatic Neoplasms, Apoptosis, In Vitro Techniques, Urokinase-Type Plasminogen Activator, Receptors, Urokinase Plasminogen Activator, Tumor Burden, Mice, Inbred C57BL, Mice, Cell Movement, Culture Media, Conditioned, Mutation, Tumor Cells, Cultured, Animals, RC254-282, Neoplasm Transplantation, Cell Proliferation
Male, Mice, Knockout, Neovascularization, Pathologic, Macrophages, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prostatic Neoplasms, Apoptosis, In Vitro Techniques, Urokinase-Type Plasminogen Activator, Receptors, Urokinase Plasminogen Activator, Tumor Burden, Mice, Inbred C57BL, Mice, Cell Movement, Culture Media, Conditioned, Mutation, Tumor Cells, Cultured, Animals, RC254-282, Neoplasm Transplantation, Cell Proliferation
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).55 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!