Novel Patents and Cancer Therapies for Transforming Growth Factor- Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis
Jelena Krstic, Irina Maslovaric and Juan F. Santibanez
Affiliation: Institute for Medical Research, University of Belgrade, Dr Subotica 4, 11129 Belgrade, Serbia.
Keywords: Cancer, patents, transforming growth factor-beta (TGF-β), transforming growth factor-beta receptors (TBRs),
urokinase type plasminogen activator (uPA), urokinase type plasminogen receptor (uPAR).
Transforming growth factor beta (TGF-β) plays different roles in health and disease. TGF-β 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-β regulates uPA expression in cancer cells while uPA, by conversion of plasminogen to active form,
plasmin, may release TGF-β 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-β 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-β in tumorigenesis, the aim of
this review is to expose the potentiality of TGF-β and uPA systems as becoming combinatorial targets for therapies and
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