Mammary tumors of dogs and the cancer stem cell theory: a comparative and translational approach

• Grant number: 14/02493-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: December 01, 2014 - November 30, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Heidge Fukumasu
• Grantee: Heidge Fukumasu
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated researchers: Daniel Diniz de Carvalho ; Enio Ferreira ; Flávio Vieira Meirelles ; Geovanni Dantas Cassali ; José Bento Sterman Ferraz ; Maria Lucia Zaidan Dagli ; Ricardo de Francisco Strefezzi ; Silvia Regina Rogatto
• Associated grant(s): 15/00601-0 - Multi-user equipament approved in grant 2014/02493-7: S3 cell sorter (Bio-rad, USA), AP.EMU
• Associated scholarship(s): 19/01234-1 - Identification of functional variants of the type SNP, indels and isoforms of alternative splicing associated with feed efficiency in Nelore cattle, BP.MS; 18/25236-0 - Uncovering the origin of multicentric canine mastocitomas: a mutational analysis, BP.IC; 18/06216-9 - Characterization of the oncolytic activity of avian paramyxovirus serotype 1 in mammary cancer cells of female dogs, BP.IC; + associated scholarships 17/15406-3 - Extracellular vesicles as potencial predictive marker in canine multicentric lymphoma, BP.MS; 17/11966-4 - Epigenetic modulations and self-renewal potential of canine mammary cancer cells: the search for potential therapeutic targets, BP.DR; 16/19307-7 - Characterization of neoantigens associated to epithelial-mesenchymal transition as potential immunotherapeutic targets, BP.PD; 16/03465-2 - Evaluation of the potential mechanisms responsible for intrinsic resistance to chemotherapy drugs and their possible association with the epithelial or mesenchymal phenotype in canine mammary carcinomas cells, BP.IC; 15/10036-8 - Assessment of Lin28a/b>let-7 pathway in cell culture isolated from canine mammary carcinoma, BP.IC - associated scholarships

Abstract

Nowadays, cancer is one of the major concerns in medical science and as a consequence, one of the foremost research topics. In dogs, cancer is responsible for 50% of deaths in animals with more than 10 years old. Mammary tumors are the most frequent in women (32%) as are in bitches (52%). Mammary tumors in those species share several similarities as histological and genetic profile, molecular targets, biological behavior and response to conventional therapies, making these spontaneous tumors interesting to characterize and turning possible the integration of pet animals with cancer in the development of cancer drugs, reducing time and costs. Therefore, the aim here is to research in a logical and coherent way, basing in current hypotheses and using modern tools, understand the complex biology of the development of mammary tumors turning possible a fast and accurate determination of new biomarkers for prediction and prognosis, in addition to generate new molecular targets that envisage the treatment and why not, prevention of these tumors. (AU)

Scientific publications

(23)

(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)

MACEDO MOTA, LUCIO FLAVIO; BONAFE, CRISTINA MOREIRA; ALEXANDRE, PAMELA ALMEIDA; SANTANA, MIGUEL HENRIQUE; NOVAIS, FRANCISCO JOSE; TORIYAMA, ERIKA; PIRES, ALDRIN VIEIRA; SILVA, SAULO DA LUZ; LEME, PAULO ROBERTO; STERMAN FERRAZ, JOSE BENTO; et al. Circulating leptin and its muscle gene expression in Nellore cattle with divergent feed efficiency. JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, v. 8, SEP 1 2017. (14/02493-7, 10/05650-5, 14/07566-2)

SANTOS, MARIANA RODRIGUES; PORFIRIO XAVIER, PEDRO LUIZ; LISBOA PIRES, PEDRO RATTO; ROCHETTI, ARINA LAZARO; ROSIM, DANIELE FERNANDA; SCAGION, GUILHERME PEREIRA; PIRES DE CAMPOS ZUCCARI, DEBORA APARECIDA; MUNIR, MUHAMMAD; FERREIRA, HELENA LAGE; FUKUMASU, HEIDGE. Oncolytic effect of Newcastle disease virus is attributed to interferon regulation in canine mammary cancer cell lines. VETERINARY AND COMPARATIVE ONCOLOGY, v. 19, n. 3, p. 593-601, SEP 2021. (18/06217-5, 19/05778-6, 16/19307-7, 18/06216-9, 14/02493-7)

XAVIER, PEDRO L. P.; CORDEIRO, YONARA G.; ROCHETTI, ARINA L.; SANGALLI, JULIANO R.; ZUCCARI, DEBORA A. P. C.; SILVEIRA, JULIANO C.; BRESSAN, FABIANA F.; FUKUMASU, HEIDGE. ZEB1 and ZEB2 transcription factors are potential therapeutic targets of canine mammary cancer cells. VETERINARY AND COMPARATIVE ONCOLOGY, v. 16, n. 4, p. 596-605, DEC 2018. (14/02493-7)

GARNICA, TAISMARA K.; LESBON, JESSIKA C. C.; AVILA, ANA C. F. C. M.; ROCHETTI, ARINA L.; MATIZ, OSCAR R. S.; RIBEIRO, ROANA C. S.; ZOPPA, ALINE; NISHIYA, ADRIANA T.; COSTA, MIRELA T.; DE NARDI, ANDRIGO B.; et al. Liquid biopsy based on small extracellular vesicles predicts chemotherapy response of canine multicentric lymphomas. SCIENTIFIC REPORTS, v. 10, n. 1, NOV 23 2020. (14/02493-7, 15/21829-9, 17/15406-3, 14/22887-0)

XAVIER, PEDRO L. P.; CORDEIRO, YONARA G.; ALEXANDRE, PAMELA A.; PIRES, PEDRO R. L.; SARANHOLI, BRUNO H.; SILVA, EDSON R.; MUELLER, SUSANNE; FUKUMASU, HEIDGE. An epigenetic screening determines BET proteins as targets to suppress self-renewal and tumorigenicity in canine mammary cancer cells. SCIENTIFIC REPORTS, v. 9, NOV 22 2019. (17/11966-4, 19/05778-6, 14/02493-7)

RAQUEL LOZANO GUILHARDUCCI; PEDRO LUIZ PORFIRIO XAVIER; JULIANO COELHO DA SILVEIRA; YONARA DE GOUVEIA CORDEIRO; LUIZ ROBERTO BIONDI; RICARDO DE FRANCISCO STREFEZZI; HEIDGE FUKUMASU. Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos. Ciência Rural, v. 52, n. 10, 2022-03-14. (14/02493-7, 19/05778-6, 15/10036-8, 17/11966-4)

XAVIER, PEDRO LUIZ PORFIRIO; MUELLER, SUSANNE; FUKUMASU, HEIDGE. Epigenetic Mechanisms in Canine Cancer. FRONTIERS IN ONCOLOGY, v. 10, OCT 23 2020. (19/05778-6, 17/11966-4, 14/02493-7)

CORDEIRO, YONARA G.; MULDER, LEANDRA M.; VAN ZEIJL, RENE J. M.; PASKOSKI, LINDSAY B.; VAN VEELEN, PETER; DE RU, ARNOUD; STREFEZZI, RICARDO F.; HEIJS, BRAM; FUKUMASU, HEIDGE. Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer. CANCERS, v. 13, n. 23, DEC 2021. (14/02493-7)

FANALLI, SIMARA LARISSA; SILVA, BRUNA PEREIRA MARTINS; GOMES, JULIA DEZEN; DURVAL, MARIAH CASTRO; DE ALMEIDA, VIVIAN VEZZONI; MOREIRA, GABRIEL COSTA MONTEIRO; SILVA-VIGNATO, BARBARA; AFONSO, JULIANA; FREITAS, FELIPE ANDRE OLIVEIRA; REECY, JAMES MARK; et al. RNA-seq transcriptome profiling of pigs' liver in response to diet with different sources of fatty acids. FRONTIERS IN GENETICS, v. 14, p. 14-pg., 2023-01-25. (21/06553-8, 20/10042-6, 18/15653-3, 18/26816-0, 14/02493-7, 17/25180-2, 18/26797-6)

FANALLI, SIMARA LARISSA; DA SILVA, BRUNA PEREIRA MARTINS; GOMES, JULIA DEZEN; DE ALMEIDA, VIVIAN VEZZONI; MOREIRA, GABRIEL COSTA MONTEIRO; SILVA-VIGNATO, BARBARA; AFONSO, JULIANA; FREITAS, FELIPE ANDRE OLIVEIRA; REECY, JAMES MARK; KOLTES, JAMES EUGENE; et al. Transcriptome profile of skeletal muscle using different sources of dietary fatty acids in male pigs. FUNCTIONAL & INTEGRATIVE GENOMICS, v. 23, n. 1, p. 19-pg., 2023-03-01. (21/06553-8, 20/10042-6, 18/15653-3, 18/26816-0, 14/02493-7, 17/25180-2, 18/26797-6)

MACEDO MOTA, LUCIO FLAVIO; BONAFE, CRISTINA MOREIRA; ALEXANDRE, PAMELA ALMEIDA; SANTANA, MIGUEL HENRIQUE; NOVAIS, FRANCISCO JOSE; TORIYAMA, ERIKA; PIRES, ALDRIN VIEIRA; SILVA, SAULO DA LUZ; LEME, PAULO ROBERTO; STERMAN FERRAZ, JOSE BENTO; et al. Circulating leptin and its muscle gene expression in Nellore cattle with divergent feed efficiency. JOURNAL OF ANIMAL SCIENCE AND BIOTECHNOLOGY, v. 8, p. 5-pg., 2017-09-01. (14/07566-2, 10/05650-5, 14/02493-7)

ALEXANDRE, PAMELA A.; KOGELMAN, LISETTE J. A.; SANTANA, MIGUEL H. A.; PASSARELLI, DANIELLE; PULZ, LIDIA H.; FANTINATO-NETO, PAULO; SILVA, PAULO L.; LEME, PAULO R.; STREFEZZI, RICARDO F.; COUTINHO, LUIZ L.; et al. Liver transcriptomic networks reveal main biological processes associated with feed efficiency in beef cattle. BMC Genomics, v. 16, DEC 18 2015. (14/02493-7, 14/07566-2, 12/14792-3, 14/00307-1)

CORDEIRO, Y. G.; XAVIER, P. L. P.; ROCHETTI, A. L.; ALEXANDRE, P. A.; MORI, C. M. C.; STREFEZZI, R. F.; FUKUMASU, H.. Transcriptomic profile reveals molecular events associated to focal adhesion and invasion in canine mammary gland tumour cell lines. VETERINARY AND COMPARATIVE ONCOLOGY, v. 16, n. 1, p. E89-E98, MAR 2018. (14/02493-7)

DE SOUZA, CAMILLA; COELHO, MARIANA; ANTONELO, DANIEL SILVA; PASSARELLI, DANIELLE; ROCHETTI, ARINA LAZARO; FUKUMASU, HEIDGE; ALMEIDA LEITE-DELLOVA, DEISE CARLA. Nephrin and podocin mRNA detection in urine sediment of dogs with chronic kidney disease: preliminary observations. JOURNAL OF VETERINARY RESEARCH, v. 66, n. 2, p. 8-pg., 2022-04-22. (14/02493-7, 19/03651-9)

FANALLI, SIMARA LARISSA; MARTINS DA SILVA, BRUNA PEREIRA; GOMES, JULIA DEZEN; DE ALMEIDA, VIVIAN VEZZONI; OLIVEIRA FREITAS, FELIPE ANDRE; MONTEIRO MOREIRA, GABRIEL COSTA; SILVA-VIGNATO, BARBARA; AFONSO, JULIANA; REECY, JAMES; KOLTES, JAMES; et al. Differential Gene Expression Associated with Soybean Oil Level in the Diet of Pigs. ANIMALS, v. 12, n. 13, p. 21-pg., 2022-07-01. (17/25180-2, 18/26797-6, 14/02493-7, 20/14148-3, 20/10042-6, 18/26816-0, 18/15653-3)

FANALLI, SIMARA LARISSA; MARTINS DA SILVA, BRUNA PEREIRA; GOMES, JULIA DEZEN; CICONELLO, FERNANDA NERY; DE ALMEIDA, VIVIAN VEZZONI; OLIVEIRA FREITAS, FELIPE ANDRE; MONTEIRO MOREIRA, GABRIEL COSTA; SILVA-VIGNATO, BARBARA; AFONSO, JULIANA; REECY, JAMES; et al. Effect of dietary soybean oil inclusion on liver-related transcription factors in a pig model for metabolic diseases. SCIENTIFIC REPORTS, v. 12, n. 1, p. 10-pg., 2022-06-20. (17/25180-2, 18/26797-6, 14/02493-7, 18/15653-3, 18/26816-0, 20/10042-6)

CORDEIRO, YONARA DE GOUVEIA; ROCHETTI, ARINA LAZARO; SOUZA, VINICIUS CASTRO; DA SILVA, EDSON ROBERTO; SCATOLINI, ANTONIO MARCIO; GENOVESE, MARIA INES; YASUI, GEORGE SHIGUEKI; FUKUMASU, HEIDGE. Antineoplastic Effect of Procyanidin-rich Extract of Lafoensia Pacari in Lung Carcinoma Cells. Brazilian Archives of Biology and Technology, v. 62, 2019. (14/02493-7)

PULZ, LIDIA H.; BARRA, CAMILA N.; ALEXANDRE, PAMELA A.; HUETE, GREICE C.; CADROBBI, KARINE G.; NISHIYA, ADRIANA T.; DE FREITAS, SILVIO HENRIQUE; FUKUMASU, HEIDGE; STREFEZZI, RICARDO F.. Identification of two molecular subtypes in canine mast cell tumours through gene expression profiling. PLoS One, v. 14, n. 6, JUN 19 2019. (13/13252-8, 14/02493-7)

ALEXANDRE, PAMELA A.; NAVAL-SANCHEZ, MARINA; PORTO-NETO, LAERCIO R.; FERRAZ, JOSE BENTO S.; REVERTER, ANTONIO; FUKUMASU, HEIDGE. Systems Biology Reveals NR2F6 and TGFB1 as Key Regulators of Feed Efficiency in Beef Cattle. FRONTIERS IN GENETICS, v. 10, MAR 22 2019. (17/14707-0, 15/22276-3, 14/07566-2, 14/02493-7)

FONSECA, LEYDIANA D.; ELER, JOANIR P.; PEREIRA, MIKAELE A.; ROSA, ALESSANDRA F.; ALEXANDRE, PAMELA A.; MONCAU, CRISTINA T.; SALVATO, FERNANDA; ROSA-FERNANDES, LIVIA; PALMISANO, GIUSEPPE; FERRAZ, JOSE B. S.; et al. Liver proteomics unravel the metabolic pathways related to Feed Efficiency in beef cattle. SCIENTIFIC REPORTS, v. 9, MAR 29 2019. (14/04937-0, 14/12492-8, 14/07566-2, 14/02493-7)

ALMEIDA, V. V.; SILVA, J. P. M.; SCHINCKEL, A. P.; MEIRA, A. N.; MOREIRA, G. C. M.; GOMES, J. D.; POLETI, M. D.; DARGELIO, M. D. B.; PATINHO, I; CONTRERAS-CASTILLO, C. J.; et al. Effects of increasing dietary oil inclusion from different sources on growth performance, carcass and meat quality traits, and fatty acid profile in genetically lean immunocastrated male pigs. LIVESTOCK SCIENCE, v. 248, JUN 2021. (14/02493-7)

CHAGAS LESBON, JESSIKA CRISTINA; GARNICA, TAISMARA KUSTRO; PORFIRIO XAVIER, PEDRO LUIZ; ROCHETTI, ARINA LAZARO; REIS, RUI MANUEL; MULLER, SUSANNE; FUKUMASU, HEIDGE. A Screening of Epigenetic Therapeutic Targets for Non-Small Cell Lung Cancer Reveals PADI4 and KDM6B as Promising Candidates. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 19, p. 16-pg., 2022-10-01. (14/02493-7, 13/08135-2)

NOVAIS, FRANCISCO JOSE; LISBOA PIRES, PEDRO RATTO; ALEXANDRE, PAMELA ALMEIDA; DROMMS, ROBERT A.; IGLESIAS, AMADEU HOSHI; STERMAN FERRAZ, JOSE BENTO; STYCZYNSKI, MARK PHILIP-WALTER; FUKUMASU, HEIDGE. Identification of a metabolomic signature associated with feed efficiency in beef cattle. BMC Genomics, v. 20, JAN 7 2019. (15/01059-4, 14/07566-2, 14/02493-7)