Format

Send to

Choose Destination
See comment in PubMed Commons below
Antioxid Redox Signal. 2014 Jul 10;21(2):221-36. doi: 10.1089/ars.2013.5690. Epub 2014 Apr 10.

Broad phenotypic changes associated with gain of radiation resistance in head and neck squamous cell cancer.

Author information

1
1 Section on Molecular Medicine, Department of Internal Medicine, Wake Forest School of Medicine , Winston-Salem, North Carolina.

Abstract

AIMS:

The central issue of resistance to radiation remains a significant challenge in the treatment of cancer despite improvements in treatment modality and emergence of new therapies. To facilitate the identification of molecular factors that elicit protection against ionizing radiation, we developed a matched model of radiation resistance for head and neck squamous cell cancer (HNSCC) and characterized its properties using quantitative mass spectrometry and complementary assays.

RESULTS:

Functional network analysis of proteomics data identified DNA replication and base excision repair, extracellular matrix-receptor interaction, cell cycle, focal adhesion, and regulation of actin cytoskeleton as significantly up- or downregulated networks in resistant (rSCC-61) HNSCC cells. Upregulated proteins in rSCC-61 included a number of cytokeratins, fatty acid synthase, and antioxidant proteins. In addition, the rSCC-61 cells displayed two unexpected features compared with parental radiation-sensitive SCC-61 cells: (i) rSCC-61 had increased sensitivity to Erlotinib, a small-molecule inhibitor of epidermal growth factor receptor; and (ii) there was evidence of mesenchymal-to-epithelial transition in rSCC-61, confirmed by the expression of protein markers and functional assays (e.g., Vimentin, migration).

INNOVATION:

The matched model of radiation resistance presented here shows that multiple signaling and metabolic pathways converge to produce the rSCC-61 phenotype, and this points to the function of the antioxidant system as a major regulator of resistance to ionizing radiation in rSCC-61, a phenomenon further confirmed by analysis of HNSCC tumor samples.

CONCLUSION:

The rSCC-61/SCC-61 model provides the opportunity for future investigations of the redox-regulated mechanisms of response to combined radiation and Erlotinib in a preclinical setting.

PMID:
24597745
PMCID:
PMC4060837
DOI:
10.1089/ars.2013.5690
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Mary Ann Liebert, Inc. Icon for PubMed Central
    Loading ...
    Support Center