α2δ1 may be a potential marker for cancer stem cell in laryngeal squamous cell carcinoma

Cancer Biomark. 2019;24(1):97-107. doi: 10.3233/CBM-181947.

Abstract

Cancer stem cells (CSCs) have the ability to dictate tumor initiation, recurrence, and metastasis. Here, we examined the expression of aα2δ1+ in laryngeal cancer tissues and further determined the effect of α2δ1 on the migratory ability and tumorigenicity of laryngeal cancer cells. Immunofluorescence staining revealed that α2δ1 was positive in 13 (13/16, 81.25%) cases in laryngeal squamous cell carcinoma (LSCC) tissues, 7 (7/16, 43.75%) cases in paracancerous tissues and only 2 (2/16, 12.5%) cases in normal tumor tissues. Our quantitative RT-PCR assays further showed that α2δ1+ LSCC cells expressed significantly higher levels of stem cell-associated genes and drug efflux and resistance genes versusα2δ1- cells. Sphere-forming assays demonstrated higher sphere-forming efficiency in the α2δ1+versusα2δ1- subpopulation. Our Matrigel assays showed that α2δ1+ cells exhibited significantly greater invasive and migratory ability than α2δ1- cells. Furthermore, the percentage of purified α2δ1+ in TU686 and TU212 cells treated cisplatin or paclitaxel was significantly higher than that of the control group. Tumor xenograft assays revealed that the tumorigenicity of α2δ1+ cells was much higher than α2δ1- cells. In conclusion, a α2δ1+ subpopulation with CSC-like property was present in laryngeal cancer and possessed high self-renewal activity and was sufficient for tumor growth, differentiation, migration, invasion, and chemotherapeutic resistance. They could represent a promising therapeutic target for LSCC.

Keywords: Laryngeal squamous cell carcinoma; cancer stem cells; α2δ1.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor
  • Calcium Channels, L-Type / genetics*
  • Calcium Channels, L-Type / metabolism
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology
  • Mice
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Prognosis
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Calcium Channels, L-Type