Abstract

PurposeTo establish penile cancer (PeCa) cell lines for the study of molecular mechanisms of carcinogenesis and testing therapeutic reagents.Materials and MethodsWe successfully established two PeCa cell lines from fresh tumor tissues from 21 cases. One cell line named Penl1 was isolated from a lymph node metastasis (LNM) of penile squamous cell carcinoma (PeSCC), usual type and comprehensively characterized here. Our in-depth characterization analysis of the Penl1 cell line included morphology, tumorigenicity, genetic characteristics, protein expression, biology, and chemosensitivity. Penl1 was authenticated by single tandem repeat (STR) DNA typing.ResultsComparative histomorphology, genetic characteristics, and protein expression patterns revealed essential similarities between the cell line and its corresponding LNM. In-depth characterization analysis of Penl1 cell line revealed tumorigenicity in immunodeficient mice, negative human papilloma virus (HPV) and mycoplasma infection, TP53 mutations and sensitivity to cisplatin and epirubicin. STR DNA typing did not match any cell lines within three international cell banks. The limitation of this study is that one patient cannot represent the complete heterogeneity of PeCa, especially primary tumor.ConclusionsWe established and characterized an HPV-negative and moderately differentiated PeCa cell model with a TP53 missense mutation from a PeSCC, usual type patient. A preliminarily study of carcinogenesis and chemosensitivity suggests that this cell model carries a tumor suppressor gene mutation and is sensitive to chemotherapy drugs.

Highlights

  • Penile squamous cell carcinoma (PeSCC) is responsible for the majority of penile cancer (PeCa), and is a rare urological cancer in developed countries, representing less than 1% of male cancers in the United States [1]

  • A preliminarily study of carcinogenesis and chemosensitivity suggests that this cell model carries a tumor suppressor gene mutation and is sensitive to chemotherapy drugs

  • In vitro cell models are indispensable for a deep understanding of carcinogenesis and metastasis; only a few cell lines isolated from primary lesions or metastasis are available for study [7,8,9,10]

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Summary

Introduction

Penile squamous cell carcinoma (PeSCC) is responsible for the majority of penile cancer (PeCa), and is a rare urological cancer in developed countries, representing less than 1% of male cancers in the United States [1]. No studies of the role of HPV in penile carcinogenesis based on cell models are currently available. In 2012, Naumann et al established a pair of cell lines from primary tumor and its corresponding LNM. They investigated the role of chemokines, chemokine receptors and podoplanin (PDPN) in this pair of cell lines [10]. These two reports provided a better understanding of tumor growth and metastasis in PeCa. In 2016, cell cultures and xenografts derived from a human verrucous penile carcinoma were established and characterization [11]. There have been no advances in the understanding of its carcinogenesis and therapeutic study, and there are no commercially available cell lines for LNM in PeCa

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