In vitro and molecular characterization of canine prostatic cells and evaluation of antitumor response against target drugs

• Grant number: 15/25400-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2016
• End date: July 31, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Renee Laufer Amorim
• Grantee: Carlos Eduardo Fonseca Alves
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 19/00765-3 - Comparative analysis of human and canine prostate cancer cells transcriptome to identify drug targets, BE.EP.PD

Abstract

The canis lupus familiaris is the only species besides humans that develops spontaneously prostate cancer (PC) associated with age and androgenic hormones. Like in humans, canine PC was associated to pre-neoplastic lesions: prostatic intraepithelial neoplasia (PIN) and proliferative inflammatory atrophy (PIA). The prostatic diseases were frequently observed in humans and shows similar molecular and pathological characteristics in both species. Due to the importance of the dog as a model to PC study, this research aims to establish three cell lines of canine prostate carcinomas and perform the analysis of global gene expression using microarray platforms and identify possible potential therapeutic targets. The study of global gene expression in canine prostatic tissue is unprecedented and aims to identify the main pathways involved in canine CP. Using bioinformatic tools we will identify differentially expressed genes and potential therapeutic targets for conducting in vitro tests with their inhibitory drugs. In this study, we aim to identify the effect of these drugs on tumor cells, and to elucidate pathways inhibited by the respective drugs. Therefore, the present study is divided into two steps consisting of: 1- establishment and characterization of three cultures of prostatic cells to assess the global gene expression (identifying differentially expressed genes) and identification of potential therapeutic targets. In this step we will perform an expression compared between primary tumor and the cultures in passage 1 (P1), passage 5 (P5), passage 10 (P10) and passing (P15). 2 - After identifying drug targets genes, we will carry out gene and protein expression of the respective genes and subsequently validating with in vitro tests. (AU)

Scientific publications

(10)

(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)

LAUFER-AMORIM, RENEE; FONSECA-ALVES, CARLOS EDUARDO; RIOS VILLACIS, ROLANDO ANDRE; DRIGO LINDE, SANDRA APARECIDA; CARVALHO, MARCIO; LARSEN, SIMON JONAS; MARCHI, FABIO ALBUQUERQUE; ROGATTO, SILVIA REGINA. Comprehensive Genomic Profiling of Androgen-Receptor-Negative Canine Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 7, MAR 28 2019. (15/25400-7)

VITTI GAMBIM, VICTORIA; LAUFER-AMORIM, RENEE; FONSECA ALVES, RICARDO HENRIQUE; GRIECO, VALERIA; FONSECA-ALVES, CARLOS EDUARDO. A Comparative Meta-Analysis and in silico Analysis of Differentially Expressed Genes and Proteins in Canine and Human Bladder Cancer. FRONTIERS IN VETERINARY SCIENCE, v. 7, p. 10-pg., 2020-11-16. (15/25400-7)

PRADO, MARIA CAROLINA MANGINI; MACEDO, SOFIA DE ALMEIDA LOSANT; GUIRALDELLI, GIULIA GUMIERO; DE FARIA LAINETTI, PATRICIA; LEIS-FILHO, ANTONIO FERNANDO; KOBAYASHI, PRISCILA EMIKO; LAUFER-AMORIM, RENEE; FONSECA-ALVES, CARLOS EDUARDO. Investigation of the Prognostic Significance of Vasculogenic Mimicry and Its Inhibition by Sorafenib in Canine Mammary Gland Tumors. FRONTIERS IN ONCOLOGY, v. 9, DEC 19 2019. (18/17109-9, 15/25400-7)

LAINETTI, PATRICIA DE FARIA; ZULIANI, FERNANDA; LEIS-FILHO, ANTONIO FERNANDO; FONSECA ALVES, RICARDO HENRIQUE; FONSECA-ALVES, CARLOS EDUARDO. Controlled Drug Delivery Vehicles in Veterinary Oncology: State-of-the-Art and Future Directions. PROCESSES, v. 8, n. 5, MAY 2020. (15/25400-7)

VITTI GAMBIM, VICTORIA; LAUFER-AMORIM, RENEE; FONSECA ALVES, RICARDO HENRIQUE; GRIECO, VALERIA; FONSECA-ALVES, CARLOS EDUARDO. A Comparative Meta-Analysis and in silico Analysis of Differentially Expressed Genes and Proteins in Canine and Human Bladder Cancer. FRONTIERS IN VETERINARY SCIENCE, v. 7, NOV 16 2020. (15/25400-7)

COSTA, CAMILA DOROTEA; JUSTO, ANDRE AUGUSTO; KOBAYASHI, PRISCILA EMIKO; STORY, MICHELLE M.; PALMIERI, CHIARA; AMORIM, RENEE LAUFER; FONSECA-ALVES, CARLOS EDUARDO. Characterization of OCT3/4, Nestin, NANOG, CD44 and CD24 as stem cell markers in canine prostate cancer. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 108, p. 21-28, MAR 2019. (15/25400-7, 17/25822-4)

LEIS-FILHO, ANTONIO FERNANDO; LAINETTI, PATRICIA DEFARIA; KOBAYASHI, PRISCILA EMIKO; PALMIERI, CHIARA; AMORIM, RENEE LAUFER; FONSECA-ALVES, CARLOS EDUARDO. Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer. PROSTATE, v. 81, n. 14, JUL 2021. (15/25400-7)

KOBAYASHI, PRISCILA E.; LAINETTI, PATRICIA F.; LEIS-FILHO, ANTONIO F.; DELELLA, FLAVIA K.; CARVALHO, MARCIO; CURY, SARAH SANTILONI; CARVALHO, ROBSON FRANCISCO; FONSECA-ALVES, CARLOS E.; LAUFER-AMORIM, RENEE. Transcriptome of Two Canine Prostate Cancer Cells Treated With Toceranib Phosphate Reveals Distinct Antitumor Profiles Associated With the PDGFR Pathway. FRONTIERS IN VETERINARY SCIENCE, v. 7, NOV 26 2020. (15/25400-7)

CAVALCA, ALEXANDRE MATHEUS BAESSO; BRANDI, ANDRESSA; FONSECA-ALVES, RICARDO HENRIQUE; LAUFER-AMORIM, RENEE; FONSECA-ALVES, CARLOS EDUARDO. -Glycoprotein and Androgen Receptor Expression Reveals Independence of Canine Prostate Cancer from Androgen Hormone Stimulatio. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 3, FEB 2022. (15/25400-7)

LAUFER-AMORIM, RENEE; FONSECA-ALVES, CARLOS EDUARDO; RIOS VILLACIS, ROLANDO ANDRE; DRIGO LINDE, SANDRA APARECIDA; CARVALHO, MARCIO; LARSEN, SIMON JONAS; MARCHI, FABIO ALBUQUERQUE; ROGATTO, SILVIA REGINA. Comprehensive Genomic Profiling of Androgen-Receptor-Negative Canine Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 7, p. 14-pg., 2019-03-28. (15/25400-7)