Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis
Apstrakt
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 regulat...es 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.
Ključne reči:
Cancer / patents / transforming growth factor-beta (TGF-beta) / transforming growth factor-beta receptors (TBRs) / urokinase type plasminogen activator (uPA) / urokinase type plasminogen receptor (uPAR)Izvor:
Recent Patents on Anti-Cancer Drug Discovery, 2014, 9, 3, 354-371Izdavač:
- Bentham Science Publ Ltd, Sharjah
Finansiranje / projekti:
- Regenerativni i modulatorni potencijal adultnih matičnih ćelija (RS-175062)
- Filogenetski pristup analizi molekularne evolucije visoko varijabilnih virusa - koinfekcije, interakcija virusa i domaćina (RS-175024)
DOI: 10.2174/1574892809666140512145535
ISSN: 1574-8928
PubMed: 24827562
WoS: 000346144000006
Scopus: 2-s2.0-84905649680
Institucija/grupa
Institut za medicinska istraživanjaTY - JOUR AU - Krstić, Jelena AU - Maslovarić, Irina AU - Santibanez, Juan PY - 2014 UR - http://rimi.imi.bg.ac.rs/handle/123456789/530 AB - 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. PB - Bentham Science Publ Ltd, Sharjah T2 - Recent Patents on Anti-Cancer Drug Discovery T1 - Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis EP - 371 IS - 3 SP - 354 VL - 9 DO - 10.2174/1574892809666140512145535 ER -
@article{ author = "Krstić, Jelena and Maslovarić, Irina and Santibanez, Juan", year = "2014", 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.", publisher = "Bentham Science Publ Ltd, Sharjah", journal = "Recent Patents on Anti-Cancer Drug Discovery", title = "Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis", pages = "371-354", number = "3", volume = "9", doi = "10.2174/1574892809666140512145535" }
Krstić, J., Maslovarić, I.,& Santibanez, J.. (2014). Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis. in Recent Patents on Anti-Cancer Drug Discovery Bentham Science Publ Ltd, Sharjah., 9(3), 354-371. https://doi.org/10.2174/1574892809666140512145535
Krstić J, Maslovarić I, Santibanez J. Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis. in Recent Patents on Anti-Cancer Drug Discovery. 2014;9(3):354-371. doi:10.2174/1574892809666140512145535 .
Krstić, Jelena, Maslovarić, Irina, Santibanez, Juan, "Novel Patents and Cancer Therapies for Transforming Growth Factor-Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis" in Recent Patents on Anti-Cancer Drug Discovery, 9, no. 3 (2014):354-371, https://doi.org/10.2174/1574892809666140512145535 . .