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Effect of HPSE-1 expression on the human endothelial cells proliferation and cappilary-like structures induction

Grant number: 16/20966-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2017
Effective date (End): January 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Taize Machado Augusto
Grantee:Isadora Aparecida Gheralde
Home Institution: Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil

Abstract

The prostate gland is subject to several conditions including prostatitis, benign and malignant prostate cancer that is related to a large number of non-accidental deaths among men, especially with advancing age. For these reasons there is a strong motivation for studies relate to mechanisms of regulation of their growth and physiology. The degradation of the basement membrane components and other components of the extracellular matrix is a critical step between the multiple events of the cascade that lead to metastasis, as well as providing an enabling environment for the tumor to develop. The growth of prostate tumors, as well as others, dependent on the growth of new blood vessels from preexisting vessels (angiogenesis) to nourish cancer cells. Cancers that stimulate the growth of new blood vessels are the most difficult to treat. Tumor cells degrade basement membrane components using a variety of enzymes such as heparanase-1 (HPSE-1) and matrix metalloproteinases (MMPs). The HPSE-1 is an endoglycosidase that cleaves heparan sulfate chains and its overexpression has a close relationship with tumor processes, metastatic potential, tumor vascularity and postoperative survival reduced in patients affected by cancer. Thus, this project aims to investigate the modulation of HPSE-1 expression in metastatic tumor lineage of prostate cancer (DU145) starting the sublineages DU145 (HPSE1 +) and DU145 (HPSE1-) in the induction of proliferation of human endothelial cells and the formation of blood vessel-like structures (tubing) from experiments in vitro co-culture. (AU)