| Grant number: | 16/01357-8 |
| Support Opportunities: | Regular Research Grants |
| Start date: | June 01, 2016 |
| End date: | November 30, 2018 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Maria Aparecida da Silva Pinhal |
| Grantee: | Maria Aparecida da Silva Pinhal |
| Host Institution: | Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil |
| Associated researchers: | Auro del Giglio ; Gisele Giannocco ; Helena Bonciani Nader |
Abstract
Understanding the molecular mechanisms involved in the development of tumors and tumor metastases is essential to generate knowledge that will allow the early detection and alternatives more effective for cancer treatment. Heparan sulfate proteoglycan (PGHS) plays an essential role in the tumor development processes. The enzyme heparanase (HPSE) comprises an endo-²-glucuronidase that degrades heparan sulfate and heparin chains. Oligosaccharides generated by HPSE action are able to intensify the effects of growth factors, angiogenic factors, cytokines and cell adhesion molecules, resulting in a significant increase in the cell proliferation, migration, angiogenesis and inflammation. Various types of tumors can present an overexpression of one of the member of the epidermal growth factor receptors, called HER2. At the moment, the monoclonal antibody called trastuzumab has been used for the treatment of patients with breast cancer that overexpress HER2, and demonstrated promising results with significant reduction of the tumor growth and increased survival of such patients. However, several side effects, as well as resistance to the treatment have been reported with the use of trastuzumab. Recent results published by our group showed that the antineoplastic activity of trastuzumab is dependent on heparan sulfate proteoglycan. Therefore, heparan sulfate, heparanase and HER2 represent molecules involved in carcinogenesis. Thus, this study aims to select and evaluate the possible antitumor effect of such binding peptides. The results may contribute to new alternatives for the treatment of cancer. (AU)
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