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.
Cells. 2021 Apr 06*** epublish ***
Hellen Kuasne, Luisa Matos do Canto, Mads Malik Aagaard, Juan Jose Moyano Muñoz, Camille De Jamblinne, Fabio Albuquerque Marchi, Cristovam Scapulatempo-Neto, Eliney Ferreira Faria, Ademar Lopes, Sébastien Carréno, Silvia Regina Rogatto
Department of Clinical Genetics, University Hospital of Southern Denmark-Vejle, Institute of Regional Health Research, University of Southern Denmark, 7100 Vejle, Denmark., International Research Center-A.C.Camargo Cancer Center, São Paulo 01508-010, Brazil., Institute for Research in Immunology and Cancer and Département de Pathologie et de Biologie Cellulaire, Université de Montréal, Montréal, QC H3C 3J7, Canada., Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil., Pelvic Surgery Department, A.C.Camargo Cancer Center, São Paulo 01508-010, Brazil.