In:
Cancer Science, Wiley, Vol. 105, No. 10 ( 2014-10), p. 1351-1359
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2014.105.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
Bookmarklink