Penile Cancer-Derived Cells Molecularly Characterized as Models to Guide Targeted Therapies

Autor(es):Mostrar menos -

Kuasne, Hellen ^{[1, 2]} ; Canto, Luisa Matos do ^[2] ; Aagaard, Mads Malik ^[2] ; Munoz, Juan Jose Moyano ^[1] ; Jamblinne, Camille De ^{[3, 4]} ; Marchi, Fabio Albuquerque ^[1] ; Scapulatempo-Neto, Cristovam ^{[5, 6]} ; Faria, Eliney Ferreira ^{[5, 7]} ; Lopes, Ademar ^[8] ; Carreno, Sebastien ^{[3, 4]} ; Rogatto, Silvia Regina ^[2]

Afiliação do(s) autor(es)

^[1] AC Camargo Canc Ctr, Int Res Ctr, BR-01508010 Sao Paulo - Brazil

^[2] Univ Southern Denmark, Inst Reg Hlth Res, Univ Hosp Southern Denmark Vejle, Dept Clin Genet, DK-7100 Vejle - Denmark

^[3] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7 - Canada

^[4] Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ H3C 3J7 - Canada

^[5] Barretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos - Brazil

^[6] Diagnost Amer DASA, BR-06455010 Sao Paulo - Brazil

^[7] Hosp Felicio Rocho, Urooncol & Robot Surg, BR-30110934 Belo Horizonte, MG - Brazil

^[8] AC Camargo Canc Ctr, Pelv Surg Dept, BR-01508010 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CELLS; v. 10, n. 4 APR 2021.
• Citações Web of Science: 0

Resumo

Penile cancer (PeCa) is a common disease in poor and developing countries, showing high morbidity rates. Despite the recent progress in understanding the molecular events involved in PeCa, the lack of well-characterized in vitro models precludes new advances in anticancer drug development. Here we describe the establishment of five human primary penile cancer-derived cell cultures, including two epithelial and three cancer-associated fibroblast (CAF) cells. Using high-throughput genomic approaches, we found that the epithelial PeCa derived- cells recapitulate the molecular alterations of their primary tumors and present the same deregulated signaling pathways. The differentially expressed genes and proteins identified are components of key oncogenic pathways, including EGFR and PI3K/AKT/mTOR. We showed that epithelial PeCa derived cells presented a good response to cisplatin, a common therapeutic approach used in PeCa patients. The growth of a PeCa-derived cell overexpressing EGFR was inhibited by EGFR inhibitors (cetuximab, gefitinib, and erlotinib). We also identified CAF signature markers in three PeCa-derived cells with fibroblast-like morphology, indicating that those cells are suitable models for PeCa microenvironment studies. We thus demonstrate the utility of PeCa cell models to dissect mechanisms that promote penile carcinogenesis, which are useful models to evaluate therapeutic approaches for the disease. (AU)

• Processo FAPESP: 15/25373-0 - Integração de métodos em larga escala de "omicas" em culturas celulares de câncer de pênis
• Beneficiário: Hellen Kuasne
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 13/03667-6 - Estudo funcional em carcinomas de pênis para validação de marcadores moleculares candidatos obtidos de análises globais integradas (genômica, transcriptômica e metilação do DNA)
• Beneficiário: Hellen Kuasne
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 08/57887-9 - Instituto Nacional de Oncogenômica
• Beneficiário: Luiz Paulo Kowalski
• Modalidade de apoio: Auxílio à Pesquisa - Temático