Matrix stiffness regulates the proliferation, stemness and chemoresistance of laryngeal squamous cancer cells

Int J Oncol. 2017 Apr;50(4):1439-1447. doi: 10.3892/ijo.2017.3877. Epub 2017 Feb 15.

Abstract

Increasing evidence shows that matrix stiffness plays a critical role in affecting the phenotype and behavior of tumor cells. We report that matrix stiffness significantly regulated the proliferation and chemotherapeutic response of Hep-2 cells. Increasing substrate stiffness promotes the proliferation of Hep-2 cells. When cultured on soft gels, Hep-2 cells expressed higher level of stem cell markers. Following treatment with cisplatin or 5-FU, we observed reduced apoptosis in Hep-2 cells cultured on soft supports. Sox2 is essential for the chemoresistance of Hep-2 cells cultured in soft stiffness. Our results demonstrated that Sox2 promotes chemoresistance of Hep-2 cells in soft stiffness via upregulating the expression of ABCG2. Our findings will provide a new platform for the future design of anticancer drugs based on the biophysical properties of the tumor site.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / metabolism*
  • Acrylic Resins / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Carcinoma, Squamous Cell / physiopathology*
  • Cell Culture Techniques / methods
  • Cell Line, Tumor
  • Cell Proliferation*
  • Cisplatin / pharmacology
  • Collagen / chemistry
  • Drug Resistance, Neoplasm*
  • Fluorouracil / pharmacology
  • Head and Neck Neoplasms / physiopathology*
  • Humans
  • Laryngeal Neoplasms / physiopathology*
  • Neoplasm Proteins / metabolism*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • SOXB1 Transcription Factors / metabolism*
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Acrylic Resins
  • Antineoplastic Agents
  • Neoplasm Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • polyacrylamide gels
  • Collagen
  • Cisplatin
  • Fluorouracil