The trypsin-like serine protease, urokinase-type plasminogen activator (uPA), is central in tissue remodeling processes and also strongly implicated in tumor metastasis.
In gastric cancer, FOXM1 and uPA levels were associated with tumor size, depth of invasion, tumor-node-metastasis (TNM) stage, lymph node metastasis, vessel invasion and distant metastases.
Genetic deficiency of uPA leads to a significant reduction in metastases in the murine transgenic MMTV-PyMT breast cancer model, demonstrating a causal role for uPA in cancer dissemination.
SCH66336 treatment also reduced the expression and activity of the urokinase-type plasminogen activator (uPA) and matrix metalloproteinase 2 (MMP-2), both important regulators of tumor metastasis.
In this study, we describe the ability of the urokinase-type plasminogen activator receptor (uPAR) promoter to efficiently and selectively target pancreatic tumors and metastases, which enables the successful management of pancreatic cancer.
Of the locally recurrent hormone-refractory tumours, 21% had an increased copy number of uPA, but no high-level amplifications were found; 31% of the metastases had increased copy number and one high-level amplification of the uPA.
These results suggest that at least one of the underlying mechanisms of BRMS1-dependent suppression of tumor metastasis includes inhibition of NF-kappaB activity and subsequent suppression of uPA expression in breast cancer and melanoma cells.
Regulated expression with highest level expression on metastases is a feature that hC4.4 A shares with the urokinase-type plasminogen activator receptor.