title: Cancer-associated fibroblasts do not respond to combined irradiation             and kinase inhibitor treatment.
abstract: The emergence of radioresistance is a significant issue in the treatment             of squamous cell carcinoma. We recently demonstrated that post-radiogenic extracellular             signal-regulated kinase (ERK) signaling might decrease radiosensitivity in this             cancer type. To further elucidate how tumor-organizing cell types respond to irradiation             and ERK pathway inhibition, we analyzed one oral squamous cell carcinoma and one             lung cancer cell line (HNSCCUM-02T, A549), fibroblasts (NIH3T3), primary normal             and cancer-associated fibroblasts (CAFs) in vitro. Irradiated cells treated with             mitogen-activated protein kinase (MAPK) inhibitor U0126 were screened for pERK             levels. Post-radiogenic cellular responses were functionally analyzed by proliferation             and colony assays. We found analogous pERK expression, proliferation and survival             of tumor and normal fibroblast cells. CAFs did not show any response to treatment.             We hypothesized that radiation and MAPK inhibition have no dose-limiting effect             on tumor-surrounding normal tissue. As CAFs are considered to influence the radioresponse             of the entire tumor, but are not affected by treatment themselves, potential CAF-mediated             tumor protection should be considered in further studies.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University, D-55101 Mainz, Germany. annette.affolter@web.de
authors.forename: Annette
authors.initials: A
authors.lastname: Affolter
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.forename: Wolf J
authors.initials: WJ
authors.lastname: Mann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Brieger
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000628:therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D009062:Mouth Neoplasms / Q000201:enzymology / Q000628:therapy*; D041681:NIH 3T3 Cells; D009570:Nitriles / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011829:Radiation Dosage; D011836:Radiation Tolerance; D014410:Tumor Stem Cell Assay
chemical_list: D002070:Butadienes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases