Characterization of stem-like cancer cells in basal cell carcinoma and its surgical margins

Exp Dermatol. 2018 Oct;27(10):1160-1165. doi: 10.1111/exd.13755. Epub 2018 Aug 20.

Abstract

Background: Understanding the pathogenesis of basal cell carcinoma (BCC) and identifying the cells responsible for propagation and recurrence are crucial for the development of new treatment strategies. The aim of this study was to characterize the cells isolated from BCC and its margin.

Methods: Primary cultures were established from 10 BCCs, their respective close resection margins (3 mm) and 10 control tissues. Stem cell markers analysis was carried out by real-time PCR and/or flow cytometry. Spheroid formation and MTT assays were also performed.

Results: Real-time PCR showed a higher expression of embryonic (Oct4, Sox2 and Nanog) and mesenchymal (CD44 and CD73) stem cell markers in tumors compared to margins and controls (P < 0.05). Bmi-1 and GPR49 were also upregulated in tumors in comparison with margins. Both tumor and margin cells, but not normal, had the capacity to form spheroids. During passages, the number of spheres increased, while the diameter decreased. Tumor cells showed higher chemo-resistance compared to margin and control cells.

Conclusions: Basal cell carcinomas expressed stem cell markers, pointing to the existence of a cancer cell side population with stemness characteristics. Margin also appeared to harbour a small number of cancer-initiating cells.

Keywords: basal cell carcinoma; embryonic and mesenchymal markers; neoplastic stem cells; surgical margin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / genetics
  • Antineoplastic Agents / pharmacology
  • Biomarkers / metabolism
  • Carcinoma, Basal Cell / pathology*
  • Carcinoma, Basal Cell / surgery
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Fluorouracil / pharmacology
  • GPI-Linked Proteins / genetics
  • Gene Expression
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Margins of Excision*
  • Nanog Homeobox Protein / genetics
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Neoplastic Stem Cells / physiology
  • Octamer Transcription Factor-3 / genetics
  • Polycomb Repressive Complex 1 / genetics
  • Primary Cell Culture
  • RNA / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • SOXB1 Transcription Factors / genetics
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery
  • Spheroids, Cellular
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • BMI1 protein, human
  • Biomarkers
  • CD44 protein, human
  • GPI-Linked Proteins
  • Hyaluronan Receptors
  • LGR5 protein, human
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Receptors, G-Protein-Coupled
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • RNA
  • Polycomb Repressive Complex 1
  • 5'-Nucleotidase
  • NT5E protein, human
  • Cisplatin
  • Fluorouracil