Osteopontin-integrin α(v)β(3) axis is crucial for 5-fluorouracil resistance in oral squamous cell carcinoma

FEBS Lett. 2015 Jan 16;589(2):231-9. doi: 10.1016/j.febslet.2014.12.004. Epub 2014 Dec 10.

Abstract

Clinical applications of a chemotherapeutic agent, 5-fluorouracil (5-FU) in oral squamous cell carcinoma (OSCC) have been limited because of drug resistance. This study aimed to identify novel mechanisms of 5-FU resistance. Here we found increased osteopontin (OPN) gene expression in OSCC tissues with resistance to 5-FU-based chemoradiotherapy. OPN overexpression in OSCC cells led to 5-FU resistance and abrogated the prosurvival effect of the drug in a mouse xenograft model. OPN-induced 5-FU resistance required integrin αvβ3. Targeting integrin αvβ3 reversed the resistance in a 5-FU-resistant clone highly expressing OPN. Our data suggest that the OPN-integrin αvβ3 axis is crucial for 5-FU resistance in OSCC.

Keywords: Cancer; Chemotherapeutic agents; Drug resistance; Osteopontin overexpression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Drug Resistance, Neoplasm*
  • Female
  • Fluorouracil / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alphaVbeta3 / metabolism*
  • Male
  • Mice, Inbred BALB C
  • Middle Aged
  • Mouth Neoplasms / genetics
  • Mouth Neoplasms / metabolism*
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • Tumor Cells, Cultured

Substances

  • Integrin alphaVbeta3
  • Osteopontin
  • Fluorouracil