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

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*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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.

Original languageEnglish
Article number814
JournalCells
Volume10
Issue number4
Number of pages20
ISSN2073-4409
DOIs
Publication statusPublished - 6. Apr 2021

Keywords

  • CAFs
  • cancer cell models
  • EGFR inhibitors
  • genomic profile
  • penile cancer
  • protein expression
  • translatomic profile

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