Open AccessGuanine nucleotide‐binding protein 1 is one of the key molecules contributing to cancer cell radioresistance
Author(s) -
Fukumoto Motoi,
Amanuma Tatsuya,
Kuwahara Yoshikazu,
Shimura Tsutomu,
Suzuki Masatoshi,
Mori Shiro,
Kumamoto Hiroyuki,
Saito Yohei,
Ohkubo Yasuhito,
Duan Zhenfeng,
Sano Kenji,
Oguchi Tomohiro,
Kainuma Kazuyuki,
Usami Shinichi,
Kinoshita Kengo,
Lee Inchul,
Fukumoto Manabu
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12489
Subject(s) - radioresistance , gene knockdown , cancer research , cancer cell , cancer , radiation therapy , cancer stem cell , biology , in vitro , cell culture , medicine , microbiology and biotechnology , genetics
Standard fractionated radiotherapy for the treatment of cancer consists of daily irradiation of 2‐Gy X‐rays, 5 days a week for 5–8 weeks. To understand the characteristics of radioresistant cancer cells and to develop more effective radiotherapy, we established a series of novel, clinically relevant radioresistant ( CRR ) cells that continue to proliferate with 2‐Gy X‐ray exposure every 24 h for more than 30 days in vitro . We studied three human and one murine cell line, and their CRR derivatives. Guanine nucleotide‐binding protein 1 ( GBP 1 ) gene expression was higher in all CRR cells than their corresponding parental cells. GBP 1 knockdown by si RNA cancelled radioresistance of CRR cells in vitro and in xenotransplanted tumor tissues in nude mice. The clinical relevance of GBP 1 was immunohistochemically assessed in 45 cases of head and neck cancer tissues. Patients with GBP 1‐positive cancer tended to show poorer response to radiotherapy. We recently reported that low dose long‐term fractionated radiation concentrates cancer stem cells ( CSC s). Immunofluorescence staining of GBP 1 was stronger in CRR cells than in corresponding parental cells. The frequency of Oct4‐positive CSC s was higher in CRR cells than in parental cells, however, was not as common as GBP 1‐positive cells. GBP 1‐positive cells were radioresistant, but radioresistant cells were not necessarily CSC s. We concluded that GBP 1 overexpression is necessary for the radioresistant phenotype in CRR cells, and that targeting GBP 1‐positive cancer cells is a more efficient method in conquering cancer than targeting CSC s.