Abstract 2355: Penile cancer in vitro models useful for the identification of targeted therapies
Authors: Hellen Kuasne, Mateus Barros-Filho, Juan Muñoz, Fabio Marchi, Cristovam Scapulatempo-Neto, Eliney Faria, Gustavo Guimarães, Ademar Lopes, Julia Mello, Maria Domingues, Sebastien Carréno, Silvia Rogatto
Journal: Cancer Research (2018)

Abstract Background: Penile carcinoma (PeCa) is a frequent disease in poor and developing countries showing high morbidity. Despite the recent progress in the molecular research of PeCa, the lack of well-characterized in vitro models precludes new advances in the knowledge of cellular processes and in preclinical tests for anticancer drugs' efficacy. Material and Methods: Twenty PeCa were surgically removed, dissected and cultured in vitro (2D and 3D environment) using 3 KSFM: 1 DMEM/F12. We established five penile cancer cell cultures in vitro (passage 20), which were characterized by genomic (CytoScan HD - Affymetrix), translatomic (Clariom D Array - Affymetrix), epigenomic (Infinium Methylation EPIC BeadChip - Illumina) and proteomic profiles (Reverse phase protein array - RPPA). Chemosensitivity assay using cisplatin and EGFR inhibitors (Erbitux and Tarceva) was performed by MTT test. Results: Two cell cultures presented typical epithelial cell morphology and epithelial markers expression such as cytokeratin and EpCAM and three were cancer-associated fibroblasts (CAFs). These cell cultures presented cancer behavior features including anchorage-independent growth, invasive potential, and capability to form tumor in nude mice. The genomic analysis revealed high similarity between the primary tumor and its derived cell culture. Transcriptomic and proteomic analysis revealed that the most relevant differentially expressed genes and proteins are components of key oncogenic pathways (MMPs, EGFR, STAT3, and PI3K/AKT/mTOR), supporting our previous data using PeCa fresh tissues. We also identified a set of genes potentially regulated by epigenetic modifications. A chemosensitivity investigation suggested that these cells are sensitive to cisplatin, a chemotherapy agent commonly used in advanced PeCa. One cell culture with EGFR overexpression was sensitive to anti-EGFR drugs (Tarceva and Erbitux). Conclusion: In general, PeCa cell cultures recapitulated cancer behavior in vitro and showed the same dysregulated pathways than their corresponding primary tumors. These cells proved to be reliable in vitro models to dissect mechanisms promoting penile carcinogenesis and to test new targeted therapies. Our results support recent studies in which patients with advanced PeCa expressing EGFR can benefit from the treatment with EGFR-targeted therapies. Citation Format: Hellen Kuasne, Mateus Barros-Filho, Juan Muñoz, Fabio Marchi, Cristovam Scapulatempo-Neto, Eliney Faria, Gustavo Guimarães, Ademar Lopes, Julia Mello, Maria Domingues, Sebastien Carréno, Silvia Rogatto. Penile cancer in vitro models useful for the identification of targeted therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2355.