Clinically relevant radioresistant cell line: a simple model to understand cancer radioresistance

Abstract

Radiotherapy (RT) is one of the major modalities for the treatment of human cancers and has been established as an excellent local treatment for malignant tumors. Conventional fractionated RT consists of 2-Gy X-rays, fractionated once a day, 5 days a week for 5-7 weeks in total 60 Gy. The efficacy of RT depends on the existence of radioresistant cells, which remains one of the most critical obstacles in RT and radio-chemotherapy. To improve the efficacy of RT, understanding the characteristics of radioresistant cells is one of the important subjects in radiation biology. Several studies have been reported to find out molecules implicated in radioresistance. However, it is noteworthy that cellular radioresistance has been mainly studied among cells with different genetic backgrounds and different origins. Therefore, making a system to compare between radioresistant and sensitive cells with the isogenic background is required. In this review, some aspects of cellular radioresistance mainly focusing on clinically relevant radioresistant (CRR) cell lines that can continue to proliferate even under exposure to 2-Gy X-rays, once a day, for more than 30 days, which is consistent with the conventional fractionated RT are discussed.

Clinically relevant radioresistant cells exhibit resistance to H2O2 by decreasing internal H2O2 and lipid peroxidation

“…It has been reported that a low mtDNA copy number in laryngeal cancer patients is associated with poor prognosis, 25 an observation that shows a possible connection between low mtDNA copy number and resistance to anticancer reagents. The decrease we found in mitochondrial membrane potential and superoxide production in CRR cells ( Figure S2) is in agreement with a previous study 14 and suggests that mitochondrial dysfunction in CRR cells could cause a reduction in ATP, influencing ion gradient formation. In this study, ATPase expression differed between parental and CRR cells (Figure 2(c) and (d)), and membrane potential was lower in CRR cells than in parental cells ( Figure 3).…”

Enhanced Expression of IGFBP-3 Reduces Radiosensitivity and Is Associated with Poor Prognosis in Oral Squamous Cell Carcinoma

“…To address the biological importance of IGFBP-3 in radiosensitivity, we employed clinically relevant radioresistant (CRR) OSCC cells [18]. Modified high-density survival (HDS) assays suggested that CRR cell line survival (both SAS-R and HSC2-R) was significantly enhanced compared with that of the corresponding parental cells under all exposure doses (Supplementary Figure S2).…”

“…In the present study, HSC-2 cells were simply designated HSC2. The CRR cell lines SAS-R and HSC2-R were derived from SAS and HSC2 cells, respectively, by exposing cells to gradually increasing X-ray doses [18,20]. These cells continued to proliferate with daily 2-Gy irradiation for more than 30 days in vitro and were resistant to irradiation.…”

Clinically relevant radioresistant rhabdomyosarcoma cell lines: functional, molecular and immune-related characterization

“…Notwithstanding several studies have identified molecular mechanisms implicated in radioresistance, the largest part has been performed by using cancer cells with different grade of radio-resistance, genetic backgrounds and origins. On the other hand, as recently suggested, biological systems able to compare radioresistant and sensitive cells with the same isogenic background should be preferred [6,9].…”