Expression of syndecan and syntenin-1 in the prostate cancer: study in two models of knockouts mice (Pten-/- and Rb1-/- Tpr53-/-) and human prostate

Author(s)

Nilton José dos Santos

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2018-04-03

Examining board members

Sérgio Luis Felisbino; Hernandes Faustino de Carvalho; Giovana Rampazzo Teixeira

• Advisor: Sérgio Luis Felisbino

Abstract

Prostate cancer (PCa) is the second most frequent and the second highest rate of morbidity and mortality among men. Studies highlight the role of cell surface proteoglycans, such as the syndecan family on initiation and progression of CaP. This study aimed to characterize the gene expression pattern and tissue localization of of the Syndecans proteoglycan family (SDCs) and Syntenin-1 binding protein in normal prostatic tissue and PCa from knockout mice and human. Gene expression analysis of these 5 genes in the different normal and tumor prostate lobes of two transgenic knockout mouse models, one deficient in the Pten gene (Pten model - produces tumors in the differentiated, invasive, indolent and non-metastatic adenocarcinoma pattern) and another deficient in both Trp53 (p53 protein) and Rb1 (Rb protein) genes (p53/Rb model - undifferentiated, neuroendocrine, invasive and metastatic tumors) in the prostatic epithelium was performed by meta-analysis of transcriptomas already deposited in the NCBI GEO database (GSE94574). Samples included in paraffin from different tumors of the two knockout models and human prostate were submitted to immunohistochemistry for laminin, smooth muscle alpha-actin, SDCs and Syntenin-1. Analysis of gene expression of the different SDCs and syntenin-1 demonstrated a similar gene expression level of the 4 SDCs and Syntenin-1 by the 4 normal mouse prostatic lobes, in which anterior prostatic lobe showed the lowest level of expression of the 5 genes studied. In the Pten knockout mice tumors, there was a significant increase in the expression of SDC1 and SDC4 in the all prostatic lobes. In the p53/Rb knockout mice tumors, there were an expressive increase in SDC3 gene expression level and a significant reduction in the expression of SDC2 and SDC4. No significant changes were observed in Syntenin-1 expression in the tumors of the two knockout mice. Regarding the tissue distribution of these 5 proteins, it was observed that the SDCs and syntenin-1 present localization in prostatic epithelial cells and stromal cells, both under normal conditions and in tumor conditions in both models and in 4 lobes, without significant alterations in this distribution during tumor progression and did not present a direct correlation with the pattern of gene expression. In human prostates, SDCs and syntenin-1 showed variable expression in epithelial and stromal cells, with tumors being positive and others negative, but a correlation with worse prognosis and lower survival was observed for SDCs 2 and 3. Our results suggest that the expression of SDC1 and SDC4 may be related to indolent tumors and in patients with better prognosis. SDC2 and, especially, SDC3 may be involved in more aggressive tumors, such as neuroendocrine tumors, and worse prognosis for patients (AU)

• FAPESP's process: 15/26175-7 - Stromal alterations in prostate cancer: a study on Syndecan proteoglycans family in two knockout mouse model - PTEN-/- e Rb1-/- Trp53-/-
• Grantee: Nilton José dos Santos
• Support Opportunities: Scholarships in Brazil - Master