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Heparan sulfate, heparanase and HER2 binding peptides with potential antineoplastic effect

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)

Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RODRIGUES-JUNIOR, DORIVAL MENDES; DE ANDRADE PELARIN, MARIA FERNANDA; NADER, HELENA BONCIANI; VETTORE, ANDRE LUIZ; SILVA PINHAL, MARIA APARECIDA. MicroRNA-1252-5p Associated with Extracellular Vesicles Enhances Bortezomib Sensitivity in Multiple Myeloma Cells by Targeting Heparanase. ONCOTARGETS AND THERAPY, v. 14, p. 455-467, 2021. Web of Science Citations: 0.
CARINA MUCCIOLO MELO; HENRIQUE PEREIRA PRADO; GABRIELA ARAÚJO ATTIE; DANIEL LACAZ RUIZ; MANOEL JOÃO BATISTA CASTELLO GIRÃO; MARIA APARECIDA DA SILVA PINHAL. In silico investigation of heparanase-correlated genes in breast cancer subtypes. Einstein (São Paulo), v. 18, p. -, 2020.
MELO, CARINA MUCCIOLO; PRADO, HENRIQUE PEREIRA; ATTIE, GABRIELA ARAUJO; RUIZ, DANIEL LACAZ; BATISTA CASTELLO GIRAO, MANOEL JOAO; DA SILVA PINHAL, MARIA APARECIDA. In silico investigation of heparanase-correlated genes in breast cancer subtypes. Einstein (São Paulo), v. 18, 2020. Web of Science Citations: 0.
THEODORO, THERESE RACHELL; MATOS, LEANDRO LUONGO; CAVALHEIRO, RENAN PELLUZZI; JUSTO, GISELLE ZENKER; NADER, HELENA BONCIANI; SILVA PINHAL, MARIA APARECIDA. Crosstalk between tumor cells and lymphocytes modulates heparanase expression. JOURNAL OF TRANSLATIONAL MEDICINE, v. 17, MAR 29 2019. Web of Science Citations: 1.

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