Cancer-associated fibroblasts do not respond to combined irradiation and kinase inhibitor treatment

Affolter,Annette; Schmidtmann,Irene; Mann,Wolf J.; Brieger,Jürgen

doi:10.3892/or.2012.2180

February 2013 Volume 29 Issue 2

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February 2013 Volume 29 Issue 2

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Article

Cancer-associated fibroblasts do not respond to combined irradiation and kinase inhibitor treatment

Authors:
- Annette Affolter
- Irene Schmidtmann
- Wolf J. Mann
- Jürgen Brieger
View Affiliations / Copyright

Affiliations: Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University, D-55101 Mainz, Germany, Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center of the Johannes Gutenberg University, D-55101 Mainz, Germany
Pages: 785-790
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Published online on: December 10, 2012

https://doi.org/10.3892/or.2012.2180
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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.

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1	Affolter A, Drigotas M, Fruth K, et al: Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer. Head Neck. Feb 2–2012.(Epub ahead of print). View Article : Google Scholar
2	Guyton KZ, Liu Y, Gorospe M, Xu Q and Holbrook NJ: Activation of mitogen-activated protein kinase by H₂O₂. Role in cell survival following oxidant injury. J Biol Chem. 271:4138–4142. 1996. View Article : Google Scholar : PubMed/NCBI
3	Robinson MJ and Cobb MH: Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 9:180–186. 1997. View Article : Google Scholar : PubMed/NCBI
4	Affolter A, Fruth K, Brochhausen C, Schmidtmann I, Mann WJ and Brieger J: Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as part of a rescue mechanism. Head Neck. 33:1448–1457. 2011. View Article : Google Scholar
5	Bissell MJ and Radisky D: Putting tumours in context. Nat Rev Cancer. 1:46–54. 2001. View Article : Google Scholar : PubMed/NCBI
6	Tsai KK, Chuang JJ, Little JB and Yuan ZM: Cellular mechanisms for low-dose ionizing radiation-induced perturbation of the breast tissue microenvironment. Cancer Res. 65:6734–6744. 2005. View Article : Google Scholar : PubMed/NCBI
7	Tsai KK, Stuart J, Chuang JJ, Little JB and Yuan ZM: Low-dose radiation-induced senescent stromal fibroblasts render nearby breast cancer cells radioresistant. Radiat Res. 172:306–313. 2009. View Article : Google Scholar : PubMed/NCBI
8	Welkoborsky HJ, Jacob R, Riazimand SH, Bernauer HS and Mann WJ: Molecular biologic characteristics of seven new cell lines of squamous cell carcinomas of the head and neck and comparison to fresh tumor tissue. Oncology. 65:60–71. 2003. View Article : Google Scholar : PubMed/NCBI
9	Gupta AK, Bakanauskas VJ, Cerniglia GJ, et al: The Ras radiation resistance pathway. Cancer Res. 61:4278–4282. 2001.PubMed/NCBI
10	Chometon G and Jendrossek V: Targeting the tumour stroma to increase efficacy of chemo- and radiotherapy. Clin Transl Oncol. 11:75–81. 2009. View Article : Google Scholar : PubMed/NCBI
11	Hwang RF, Moore T, Arumugam T, et al: Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res. 68:918–926. 2008. View Article : Google Scholar : PubMed/NCBI
12	Hawasawi NM, Ghebeh H, Hendrayani SF, et al: Breast-carcinoma-associated fibroblasts and their counterparts display neoplastic-specific changes. Cancer Res. 68:2717–2725. 2008. View Article : Google Scholar
13	Madeo A and Maggiolini M: Nuclear alternate estrogen receptor GPR30 mediates 17β-estradiol-induced gene expression and migration in breast cancer-associated fibroblasts. Cancer Res. 70:6036–6046. 2010.PubMed/NCBI
14	Ohuchida K, Mizumoto K, Murakami M, et al: Radiation to stromal fibroblasts increases invasiveness of pancreatic cancer cells through tumor-stromal interactions. Cancer Res. 64:3215–3222. 2004. View Article : Google Scholar
15	Littlepage LE, Egeblad M and Werb Z: Coevolution of cancer and stromal cellular responses. Cancer Cell. 7:499–500. 2005. View Article : Google Scholar : PubMed/NCBI
16	Kalluri R and Zeisberg M: Fibroblasts in cancer. Nat Rev Cancer. 6:392–401. 2006. View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Cancer-associated fibroblasts do not respond to combined irradiation and kinase inhibitor treatment

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