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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Affolter A,Schmidtmann I,Mann WJ,Brieger J

doi

10.3892/or.2012.2180

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

785-90

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

29

pub_type

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