Role of heparanase-1 (HPSE-1) produced by prostate tumor cells in the differentiation and polarization of human monocytes (THP-1) in macrophages

• Grant number: 19/18660-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2019
• End date: May 31, 2021
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Taize Machado Augusto
• Grantee: Thais Noto Faria
• Host Institution: Faculdade de Medicina de Jundiaí (FMJ). Prefeitura Municipal de Jundiaí. Jundiaí , SP, Brazil

Abstract

The prostate gland is target of several conditions including prostatitis, benign and malignant prostate neoplasms such as cancer, which is responsible for a large number of non-accidental deaths among men, especially with advancing age. For these reasons there is great motivation for studies that refer to the mechanisms of regulation of its growth and physiology. Several investigations into prostate cancer are conducted in in vitro experimental models. There are several established cell lines derived from human prostate cancer and described in the literature such as PC3 (derived from bone prostate cancer metastasis).In addition to tumor cells, the participation of other connective tissue cells acting in cooperation is already well known. Among these cells, we highlight the key cells of the inflammatory process that reside in the tumor microenvironment, the macrophages, which have the ability to change their phenotype and polarize into two major subtypes: M1 and M2. Regarding the polarization of these cells and tumor development, the M2 phenotype is more related to tumor progression, while M1 acts to promote antitumor responses. Dense infiltrates of these cells, tumor-associated macrophages, are observed in prostate cancer, with the macrophage M2 phenotype as a significant component. The HPSE-1 molecule is related to the polarization of these leukocytes for both proinflammatory and pro-tumorigenic phenotype. HPSE-1 is an enzyme that has the ability to cleave the heparan sulfate glycosaminoglycan chains present in heparan sulfate proteoglycans, thus releasing several other molecules in the extracellular matrix, such as growth factors, angiogenics and various cytokines and chemokines. When overexpressed, in some cancers, it may initiate or augment tumor developmental processes, acting on processes involving tumor metastasis, tumor cell proliferation, and tumor neovascularization. Although HPSE-1 has been shown to influence macrophage polarization, studies on this mechanism in prostate cancer are still lacking. In this context, this project aims to investigate the participation of HPSE-1 produced by prostate tumor cells in macrophage polarization in the tumor microenvironment through THP-1 human monocyte lineage differentiation via cytokine dosage analysis, peroxidase activity and flow cytometry .