Advanced search
Start date
Betweenand

The role of proteoglycan´s microdomains-6-O-sulfated in tumor biology and tissues.

Grant number: 16/18066-6
Support type:Regular Research Grants
Duration: November 01, 2016 - April 30, 2019
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Leny Toma
Grantee:Leny Toma
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Assoc. researchers:Helena Bonciani Nader ; Nora Manoukian Forones

Abstract

Molecules from tumor microenvironment has become the purpose of intense research in cancer treatment. Proteoglycans (PGs) has been the target of these studies due to their location, as well as their structural features which contributes to their regulatory and multifactorial functions. In the previous project, we have shown the importance of 6-O-sulfation in heparan sulfate proteoglycans through the extracellular enzymes 6-O-endosulfatases, Sulf 1 and Sulf 2, which remove sulfate from the 6-O position, editing these extracellular domains. In the present project, the aim is to further investigate these enzymes expression, now in vivo, analyzing human colorectal cancer tissues and to compare to the normal adjacent ones. A second aim of this project will be to study proteoglycans from colorectal adenocarcinoma cell lines, which have also 6-O-sulfated domains, however in chondroitin sulfate chains. These molecules are denominated chondroitin sulfate E (CS-E), related in the literature with higher motility of neural cells. For this purpose, knockdown of the N-acetylgalactosamine-4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), enzyme from the biosynthesis of the CS-E will be achieved by interference RNA using shRNA. Resistant clones will be isolated and selected by Real Time PCR and western blot. The effects of GalNAc4S-6ST knockdown will be investigated by structural studies with specific enzymes, and biological assays analyzing cell proliferation, adhesion, migration and invasion. Furthermore, the involvement of CS-E in Wnt signaling will be studied because some evidence has shown recognition of CS-E and Wnt3a ligant, although this signaling pathway needs to be further investigated. Proving these results we hope to advance towards the elucidation of the role these charged molecules play in cancer biology and disease progression. (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)
LISTIK, EDUARDO; XAVIER, EVERTON GALVAO; DA SILVA PINHAL, MARIA APARECIDA; TOMA, LENY. Dermatan sulfate epimerase 1 expression and mislocalization may interfere with dermatan sulfate synthesis and breast cancer cell growth. Carbohydrate Research, v. 488, FEB 2020. Web of Science Citations: 0.
LISTIK, EDUARDO; MARQUES GASCHLER, JULIANA AZEVEDO; MATIAS, MURILO; NEUPPMANN FERES, MURILO FERNANDO; TOMA, LENY; RAPHAELLI NAHAS-SCOCATE, ANA CARLA. Proteoglycans and dental biology: the first review. Carbohydrate Polymers, v. 225, DEC 1 2019. Web of Science Citations: 0.
RAPHAELLI NAHAS-SCOCATE, ANA CARLA; ALVES DE MORAES, GABRIELLE FERRANTE; NADER, HELENA BONCIANI; VICENTE, CAROLINA MELONI; TOMA, LENY. Analysis of proteoglycan expression in human dental pulp. ARCHIVES OF ORAL BIOLOGY, v. 90, p. 67-73, JUN 2018. Web of Science Citations: 1.
VICENTE, CAROLINA MELONI; DA SILVA, DAIANA APARECIDA; SARTORIO, PRISCILA VERONICA; SILVA, TIAGO DONIZETTI; SAAD, SARHAN SYDNEY; NADER, HELENA BONCIANI; FORONES, NORA MANOUKIAN; TOMA, LENY. Heparan Sulfate Proteoglycans in Human Colorectal Cancer. ANALYTICAL CELLULAR PATHOLOGY, 2018. Web of Science Citations: 3.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.