Cancer-associated fibroblasts do not respond to combined irradiation and kinase inhibitor treatment.
Oncol Rep
; 29(2): 785-90, 2013 Feb.
Article
in En
| MEDLINE
| ID: mdl-23232940
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mouth Neoplasms
/
Carcinoma, Squamous Cell
/
Carcinoma, Non-Small-Cell Lung
/
Fibroblasts
/
Lung Neoplasms
Type of study:
Risk_factors_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2013
Document type:
Article
Affiliation country:
Germany