Effects of culture method on response to EGFR therapy in head and neck squamous cell carcinoma cells

Sci Rep. 2019 Aug 28;9(1):12480. doi: 10.1038/s41598-019-48764-3.

Abstract

The EGFR pathway plays a critical role in head and neck squamous cell carcinoma (HNSCC). Targeted therapies against the EGFR are utilized as a treatment for HNSCCC. However, patient response is heterogeneous and molecular biomarkers are lacking to predict patient response. Therefore, functional assays where drug response is directly evaluated in tumor cells are an interesting alternative. Previous studies have shown that experimental conditions modify the drug response observed in functional assays. Thus, in this work the influence of the culture environment on response to Cetuximab (EGFR monoclonal antibody) and AZD8055 (mTOR inhibitor) was evaluated. HNSCC UM-SCC-1 and UM-SCC-47 cells were cultured in 2D monoculture and compared with: 2D co-culture with cancer-associated fibroblasts (CAF); 3D culture in collagen hydrogels; and 3D culture in tumor spheroids. The results showed UM-SCC-1 drug response significantly changed in the different culture environments; leading to an increase in drug resistance in the CAF co-culture and the 3D spheroids. Conversely, UM-SCC-47 exhibited a more constant drug response across culture conditions. In conclusion, this work highlights the importance of culture conditions that modulate response to EGFR pathway inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Culture Techniques*
  • Cell Line, Tumor
  • Cetuximab / pharmacology*
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Female
  • Head and Neck Neoplasms* / drug therapy
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Male
  • Morpholines / pharmacology*
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / metabolism
  • Signal Transduction / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • Squamous Cell Carcinoma of Head and Neck* / drug therapy
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • Morpholines
  • Neoplasm Proteins
  • (5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab