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Heparanase activity and its role in the modulation of extracellular signaling in prostate development

Grant number: 12/17657-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2012
Effective date (End): August 31, 2015
Field of knowledge:Biological Sciences - Morphology
Principal Investigator:Hernandes Faustino de Carvalho
Grantee:Guilherme Oliveira Barbosa
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression, AP.TEM
Associated scholarship(s):14/18103-3 - Heparan sulfate proteoglycans in epithelial morphogenesis and physiology: knock out of Syndecan-1 using CRISPR-Cas9, BE.EP.DD


Ventral prostate morphogenesis occurs during the first three weeks of rats and involvis cavitation of the epithelial cords due to the polarization and differentiation of the epithelial cells in contact to the basal membrane that survives and the internal cells apoptosis. There is a signaling made by many extracellular factors between stroma and epithelia that controls these events. Among the factor there are some that binds to heparan sulfate such as FGF, TGF, HGF, CXCL and SHH. In this manner we believe that Heparanase-1 has a role in epithelial morphogenesis, controlling signaling through extracellular factor releasing from ECM, that takes epithelial cell to a controlled cell differentiation from proximal to distal region, formation of epithelial barrier, blocking internal cells to access growth and surviving factors, and finally taking them to cell death. In order to test this hypothesis we shall use prostate epithelial cell spheroid cultures and organ culture, associated to gene silencing tools (interference RNA), such as for heparanase and tight junction proteins. Protein stain in histologicals slices and whole mount. Genetics and biochemical analyses. Finally live cell imaging to observe epithelial barrier formation folloewd the lumen formation by apoptosis. With all this we intend to show that cell death is not associated only to anoikis, but also to extracellular factors deprivation, that had been released by heparanase, and may act in epithelial cell differentiation and polarization. (AU)

Scientific publications
(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)
BARBOSA, GUILHERME OLIVEIRA; AUGUSTO, TAIZE MACHADO; BRUNI-CARDOSO, ALEXANDRE; CARVALHO, HERNANDES F. The role of SDF1 in prostate epithelial morphogenesis. Journal of Cellular Physiology, v. 234, n. 5, p. 6886-6897, MAY 2019. Web of Science Citations: 0.
BARBOSA, GUILHERME OLIVEIRA; BRUNI-CARDOSO, ALEXANDRE; DA SILVA PINHAL, MARIA APARECIDA; AUGUSTO, TAIZE MACHADO; CARVALHO, HERNANDES F. Heparanase-1 activity and the early postnatal prostate development. DEVELOPMENTAL DYNAMICS, v. 248, n. 3, p. 211-220, MAR 2019. Web of Science Citations: 1.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
BARBOSA, Guilherme Oliveira. Heparam-sulfate/Heparanase1 axis on prostate epithelial morphogenesis. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia.

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