Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis

Abstract

Transforming growth factor beta (TGF-beta) plays different roles in health and disease. TGF-beta has been assumed as a dual factor in tumor growth, since it can repress epithelial tumor development in early stages, while it acts as a tumor promoter in the late stages of tumor progression. The cancer cells, during cancerogenesis, acquire migration and invasion capacities and finally they metastasize. The urokinase type plasminogen activator (uPA) system, comprised of uPA, the cell surface receptor (uPAR) and plasminogen-plasmin, is involved in the proteolytic degradation of the extracellular matrix and it also regulates several critical cellular events by its capacity to trigger the activation of intracellular signaling pathways. This enables the cancer cell survival, its dissemination, and enhancement of cell malignancy during tumor progression. The expression of both uPA and uPAR is finely regulated in normal development, but their expression is deregulated in cancer. TGF-beta regulates uPA expression in cancer cells while uPA, by conversion of plasminogen to active form, plasmin, may release TGF-beta from its latent state. Thus, these pathways cross-regulate each other by mutual feedback contributing to tumor progression. Here, we review the specific roles and the interplay between TGF-beta and uPA system in cancer cells, the current cancer therapies and the novel patents focused mainly on uPA and TGF-beta ligands and their cell surface receptors respectively. Finally, with regard to the mutual activity of uPA and TGF-beta in tumorigenesis, the aim of this review is to expose the potentiality of TGF-beta and uPA systems as becoming combinatorial targets for therapies and patents.