This study aimed to establish and characterize primary cell cultures and xenografts derived from penile carcinoma (PeCa) in order to provide experimental models for cellular processes and efficacy of new treatments. A verrucous squamous cell carcinoma (VSCC) was macrodissected, dissociated, and cultivated in KSFM/DF12 medium. Cell cultures were evaluated at passage 5 (P5) using migration and invasion assays and were serially propagated, in vivo, in BALB/c nude mice until passage 3 (X1-X3). Immunophenotypic characterization of cultures and xenografts was performed. Genomic (CytoScan HD, Affymetrix) and transcriptomic profiles (HTA 2.0 platform, Affymetrix) for VSCC, cell cultures, and xenografts were assessed. P5 cells were able to migrate, invade the Matrigel, and produce tumors in immunodeficient mice, demonstrating their malignant potential. The xenografts unexpectedly presented a sarcomatoid-like carcinoma phenotype. Genomic analysis revealed a high similarity between the VSCC and tumor-derived xenograft, confirming its xenograft origin. Interestingly, a subpopulation of P5 cells presented stem cell-related markers (CD44(+)CD24(-) and ALDH1(high)) and sphere-forming capacity, suggesting their potential xenograft origin. Cell cultures and xenografts retained the genomic alterations present in the parental tumor. Compared to VSCC, differentially expressed transcripts detected in all experimental conditions were associated with cellular morphology, movement, and metabolism and organization pathways. Malignant cell cultures and xenografts derived from a verrucous penile carcinoma were established and fully characterized. Nevertheless, xenograft PeCa models must be used with caution, taking into consideration the selection of specific cell populations and anatomical sites for cell/tumor implantation.
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016 Mar 10 [Epub ahead of print]
Juan J Muñoz, Sandra A Drigo, Hellen Kuasne, Rolando A R Villacis, Fabio A Marchi, Maria A C Domingues, Ademar Lopes, Tiago G Santos, Silvia R Rogatto
International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., NeoGene Laboratory, Department of Urology, Medical School, São Paulo State University-UNESP, CEP: 18.618-000, Botucatu, SP, Brazil. ., International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., Department of Pathology, Medical School, São Paulo State University-UNESP, Botucatu, SP, Brazil., Department of Pelvic Surgery, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil., International Research Center-CIPE, A. C. Camargo Cancer Center, São Paulo, SP, Brazil. .