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Abstract
Purpose: Cancer stem cells (CSCs) are relatively resistant to radiation compared to their non-tumorigenic progeny. Ionizing radiation (IR) can expand the pool of CSCs that leads to more aggressive cancers, but the reason underlying CSC-induced cancer aggressiveness after radiation therapy remains unclear. To understand this, we investigated the phenotypic and molecular characteristics of sphere cells formed from IR-treated patient-derived xenograft (PDX) lung adenocarcinoma tumors.

Materials and methods: After treatment with various modes of IR, we collected tumors from PDX mice and successfully obtained sphere cells. To compare tumorigenicity, we performed migration, invasion, and mouse transplantation assays with sphere cells from each group. To investigate the molecular features, we used a cDNA microarray and compared gene expression among groups.

Results and conclusions: Tumorigenicity assays revealed that sphere cells from 2- or 5-Gy IR-treated tumors more aggressive than sphere cells from non-IR treated tumors. Microarray results showed that SERPIB4 and CCL2 were upregulated in sphere cells from IR-treated tumors compared to that in sphere cells from non-IR treated tumors. Interestingly, these genes are related to immune reactions in cancer. Taken together, our results suggest that the aggressiveness of sphere cells obtained after IR treatment is related to resistance, and provide new opportunities for exploring targeted therapies to overcome common radioresistance.

Affiliations

Jinhyang Choi  1   2 , Eun Jung Ko  1   3 , Eun Jin Ju  1   3 , Seok Soon Park  1   3 , Jin Park  1   3 , Seol Hwa Shin  1   3 , Se Jin Jang  3   4 , Jung Shin Lee  5 , Si Yeol Song  3   6 , Seong-Yun Jeong  1   3   7 , Eun Kyung Choi  3   6
1 Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
2 Department of Medical Science, University of Ulsan College of Medicine, Seoul, Korea.
3 Center for Advancing Cancer Therapeutics, Seoul, Korea.
4 Department of Pathology, Asan Medical Center, Seoul, Korea.
5 Department of Internal Medicine, Asan Medical Center, Seoul, Korea.
6 Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
7 Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.