Isogenic radiation resistant cell lines: Development and validation strategies

McDermott, Niamh; Meunier, Armelle; Lynch, Thomas; Hollywood, Donal; Marignol, Laure

doi:10.3109/09553002.2014.873557

Cited by 22 publications

(29 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our model, the increased resistance of SW1463 RES was accompanied by elevated levels of active and total β-catenin, and increased TCF/LEF transcriptional activity. Interestingly, several of the genes described by Ahn and colleagues (24) were differentially deregulated in a similar fashion in our model, including many Wnt pathway genes. This points to an involvement of Wnt/β-catenin signaling in radiation resistance in multiple tumor entities.…”

Section: Discussionsupporting

confidence: 78%

“…To obtain further evidence that Wnt/β-catenin signaling regulates responsiveness of CRC cells to CRT, we repetitively irradiated SW1463 cells in order to establish an isogenic radioresistant cell population (Supplementary Figure S5A), an approach well described in the literature (24). As shown in Figure 4A, repeated irradiation with 2 Gy (total dose of 68 Gy after 35 weeks) resulted in the development of a SW1463 cell population with increased resistance to irradiation ( P = 0.0575), referred to as SW1463 RES .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Emons

Spitzner

Reineke

et al. 2017

Molecular Cancer Research

114

View full text Add to dashboard Cite

Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer (CRC). The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy (CRT) and TCF7L2 mediates resistance to CRT. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small molecule inhibitor (XAV-939) resulted in sensitization of CRC cells to CRT. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, non-tumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiological ligand of Frizzled-receptors, which increased resistance to CRT. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to CRT, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiation. In summary, aberrant activation of Wnt/β-catenin signaling not only regulates the development and progression of colorectal cancer, but also mediates resistance of rectal cancers to chemoradiotherapy. Implications Targeting Wnt/β-catenin signaling or one of the downstream pathways represents a promising strategy to increase response to CRT.

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Emons

Spitzner

Reineke

et al. 2017

Molecular Cancer Research

114

View full text Add to dashboard Cite

show abstract

“…Isogenic models of radioresistance have been generated through exposure of cancer cell lines to a variety of fractionation schedules with total doses within a 40–60 Gy range 20 21 22 and overall treatment times varying from 5 days 23 to 6 years 16 24 . In prostate cancer, isogenic models of LncaP, PC-3 and DU145 cells were generated through 2 Gy daily exposure over 5 consecutive days and associated with a 1.6, 1.5 and 1.5 fold increase in the radiation dose needed to induce 0.1% survival (dose modifying factor), when compared to wild type cells 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Exposure of cancer cells to fractionated radiation schedules can select a cancer subpopulation with modified cell fate in response to subsequent radiation exposure and affect tumour control probablity 15 . This selection process is increasingly reproduced in vitro to investigate the molecular response of cancer cells and guide the development of novel biomarkers of radiotherapy failure (reviewed in 16 ). Few of these isogenic models currently exist for prostate cancer.…”

mentioning

confidence: 99%

Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells

McDermott

Meunier

Mooney

et al. 2016

Sci Rep

View full text Add to dashboard Cite

The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 prostate cancer cells with fractionated 2 Gy radiation to a cumulative total dose of 60 Gy. This process selected for 22Rv1-cells with increased clonogenic survival following subsequent radiation exposure but increased sensitivity to Docetaxel. This RR-22Rv1 cell line was enriched in S-phase cells, less susceptible to DNA damage, radiation-induced apoptosis and acquired enhanced migration potential, when compared to wild type and aged matched control 22Rv1 cells. The selection of radioresistant cancer cells during fractionated radiation therapy may have implications in the development and administration of future targeted therapy in conjunction with radiation therapy.

show abstract

“…An isogenic model of radioresistance was developed by cumulative exposure of MCF-7 and MDA-MB-231 cells to 30 Gy-fractionated radiation, resulting in the generation of a subline with significantly increased survival potential compared to sham control cells, as reported previously in a model of radioresistant lung cancer cells (Arechaga-Ocampo et al, 2017). The development of isogenic chemo-and radioresistant cell lines has been used successfully to investigate the molecular changes associated with acquired resistance to therapy and tumor aggressiveness in cancer (McDermott et al, 2014). Exposure of tumors to fractionated radiation schedules can select a cancer cell subpopulation with an increased capacity to overcome the anti-proliferative effects of radiotherapy (Zaider and Hanin, 2011) by modulating the abundance and functions of molecules, including miRNAs (Arechaga-Ocampo et al, 2017;Metheetrairut and Slack, 2013;Zhang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

New insights into radioresistance in breast cancer identify a dual function of miR‐122 as a tumor suppressor and oncomiR

et al. 2019

View full text Add to dashboard Cite

Radioresistance of tumor cells gives rise to local recurrence and disease progression in many patients. MicroRNAs (miRNAs) are master regulators of gene expression that control oncogenic pathways to modulate the radiotherapy response of cells. In the present study, differential expression profiling assays identified 16 deregulated miRNAs in acquired radioresistant breast cancer cells, of which miR‐122 was observed to be up‐regulated. Functional analysis revealed that miR‐122 has a role as a tumor suppressor in parental cells by decreasing survival and promoting radiosensitivity. However, in radioresistant cells, miR‐122 functions as an oncomiR by promoting survival. The transcriptomic landscape resulting from knockdown of miR‐122 in radioresistant cells showed modulation of the ZNF611 , ZNF304 , RIPK1 , HRAS , DUSP8 and TNFRSF21 genes. Moreover, miR‐122 and the set of affected genes were prognostic factors in breast cancer patients treated with radiotherapy. Our data indicate that up‐regulation of miR‐122 promotes cell survival in acquired radioresistant breast cancer and also suggest that miR‐122 differentially controls the response to radiotherapy by a dual function as a tumor suppressor an and oncomiR dependent on cell phenotype.

show abstract

Isogenic radiation resistant cell lines: Development and validation strategies

Abstract: There is large variability in the strategies used to generate and validate isogenic models of radioresistance. Further characterization of these models is required.

Cited by 22 publications

References 80 publications

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling

Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells

New insights into radioresistance in breast cancer identify a dual function of miR‐122 as a tumor suppressor and oncomiR

Contact Info

Product

Resources

About