Prostate cancer: involvement of adiponectin and type X collagen pathways

• Grant number: 19/19644-1
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2020
• End date: October 31, 2022
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Sérgio Luis Felisbino
• Grantee: Sérgio Luis Felisbino
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated researchers: Flávio de Oliveira Lima

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 obesity and the extracellular matrix in the progression of PCa to the more aggressive, metastatic and resistant state to antiandrogenic, chemotherapeutic and radiotherapeutic therapies. Transcriptome analyzes of transgenic mouse models for prostate cancer have revealed changes in the expression of hundreds of genes, which have been confirmed in gene expression databases for human prostate tumors. In this project, we will characterize in more detail, in two subprojects, alterations in genes related to Adiponectin hormone pathway and its receptors ADIPOR1 and ADIPOR2; and the participation of extracellular matrix protein type X collagen, gene COL10A1. For this, we intend: 1) to characterize the pattern of gene and protein expression of these pathway components in human prostate tumor samples and associate with clinical data of the patients by data mining in public databases and in our own group of patients by immunohistochemistry and qPCR; 2) to evaluate the effects of Adiporon (agonist of Adiponectin receptors) administration on prostate tumor progression of TRAMP mouse model; 3) to evaluate the effects of high fat diet on growth, maturation, aging and lesions onset in the adiponectin knockout mice; 4) to perform in vitro functional studies to characterize the pattern of gene and protein expression of these pathways by normal and prostatic tumor cells (PNT-2, LNCaP, PC3, DU145) under different culture conditions, such as: exposure to agonists, inhibitors, to type X collagen protein or after transcription silencing of the mRNA for some components of these pathways; associated with viability, proliferation, migration and cell invasion assays and gene expression analysis. These results will contribute to a better understanding of the participation of these pathways in prostate cancer, to reveal data for better patient prognosis stratification and potential therapeutic targets. (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)

SANTOS, NILTON JOSE; BARQUILHA, CAROLINE NASCIMENTO; BARBOSA, ISABELA CORREA; MACEDO, RODRIGO TAVARES; LIMA, FLAVIO OLIVEIRA; JUSTULIN, LUIS ANTONIO; BARBOSA, GUILHERME OLIVEIRA; CARVALHO, HERNANDES F.; FELISBINO, SERGIO LUIS. Syndecan Family Gene and Protein Expression and Their Prognostic Values for Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 16, AUG 2021. (16/09532-3, 19/19644-1, 15/26175-7)

SANMUKH, SWAPNIL GANESH; DOS SANTOS, NILTON JOSE; BARQUILHA, CAROLINE NASCIMENTO; CUCIELO, MAIRA SMANIOTTO; DE CARVALHO, MARCIO; DOS REIS, PATRICIA PINTOR; DELELLA, FLAVIA KARINA; CARVALHO, HERNANDES F.; FELISBINO, SERGIO LUIS. Bacteriophages M13 and T4 Increase the Expression of Anchorage-Dependent Survival Pathway Genes and Down Regulate Androgen Receptor Expression in LNCaP Prostate Cell Line. Viruses-Basel, v. 13, n. 9, SEP 2021. (19/19644-1)

SANTOS, NILTON J.; CAMARGO, ANA CAROLINA LIMA; CARVALHO, HERNANDES F.; JUSTULIN, LUIS ANTONIO; FELISBINO, SERGIO LUIS. Prostate Cancer Secretome and Membrane Proteome from Pten Conditional Knockout Mice Identify Potential Biomarkers for Disease Progression. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 16, p. 26-pg., 2022-08-01. (19/19644-1, 19/05952-6)

SANTOS, NILTON J.; XIMENES, PEDRO POL; CONSTANTINO, FLAVIA BESSI; CARVALHO, HERNANDES F.; FELISBINO, SERGIO LUIS. Mucinous metaplasia in Pten conditional knockout mice and mucin family genes as prognostic markers for prostate cancer. Life Sciences, v. 293, p. 10-pg., 2022-01-29. (19/05952-6, 19/19644-1)