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HDAC inhibitor confers radiosensitivity to prostate stem-like cells

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HDAC inhibitor confers radiosensitivity to prostate stem-like cells. / Frame, F M; Pellacani, D; Collins, A T; Simms, M S; Mann, V M; Jones, Gdd; Meuth, M; Bristow, R G; Maitland, N J.

In: British journal of cancer, Vol. 109, No. 12, 10.12.2013, p. 3023-3033.

Research output: Contribution to journalArticle

Harvard

Frame, FM, Pellacani, D, Collins, AT, Simms, MS, Mann, VM, Jones, G, Meuth, M, Bristow, RG & Maitland, NJ 2013, 'HDAC inhibitor confers radiosensitivity to prostate stem-like cells', British journal of cancer, vol. 109, no. 12, pp. 3023-3033. https://doi.org/10.1038/bjc.2013.691

APA

Frame, F. M., Pellacani, D., Collins, A. T., Simms, M. S., Mann, V. M., Jones, G., ... Maitland, N. J. (2013). HDAC inhibitor confers radiosensitivity to prostate stem-like cells. British journal of cancer, 109(12), 3023-3033. https://doi.org/10.1038/bjc.2013.691

Vancouver

Frame FM, Pellacani D, Collins AT, Simms MS, Mann VM, Jones G et al. HDAC inhibitor confers radiosensitivity to prostate stem-like cells. British journal of cancer. 2013 Dec 10;109(12):3023-3033. https://doi.org/10.1038/bjc.2013.691

Author

Frame, F M ; Pellacani, D ; Collins, A T ; Simms, M S ; Mann, V M ; Jones, Gdd ; Meuth, M ; Bristow, R G ; Maitland, N J. / HDAC inhibitor confers radiosensitivity to prostate stem-like cells. In: British journal of cancer. 2013 ; Vol. 109, No. 12. pp. 3023-3033.

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@article{4b8438be9f134e5388b9fb423afcb354,
title = "HDAC inhibitor confers radiosensitivity to prostate stem-like cells",
abstract = "Background:Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction.Methods:Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrin(hi)/CD133(+)), transit-amplifying (TA, α2β1integrin(hi)/CD133(-)) and committed basal (CB, α2β1integrin(lo)) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser.Results:Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation.Interpretation:Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.",
author = "Frame, {F M} and D Pellacani and Collins, {A T} and Simms, {M S} and Mann, {V M} and Gdd Jones and M Meuth and Bristow, {R G} and Maitland, {N J}",
year = "2013",
month = "12",
day = "10",
doi = "10.1038/bjc.2013.691",
language = "English",
volume = "109",
pages = "3023--3033",
journal = "British journal of cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "12",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - HDAC inhibitor confers radiosensitivity to prostate stem-like cells

AU - Frame, F M

AU - Pellacani, D

AU - Collins, A T

AU - Simms, M S

AU - Mann, V M

AU - Jones, Gdd

AU - Meuth, M

AU - Bristow, R G

AU - Maitland, N J

PY - 2013/12/10

Y1 - 2013/12/10

N2 - Background:Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction.Methods:Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrin(hi)/CD133(+)), transit-amplifying (TA, α2β1integrin(hi)/CD133(-)) and committed basal (CB, α2β1integrin(lo)) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser.Results:Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation.Interpretation:Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.

AB - Background:Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant fraction.Methods:Primary cultures were derived from patients undergoing resection for prostate cancer or benign prostatic hyperplasia. After short-term culture, three populations of cells were sorted, reflecting the prostate epithelial hierarchy, namely stem-like cells (SCs, α2β1integrin(hi)/CD133(+)), transit-amplifying (TA, α2β1integrin(hi)/CD133(-)) and committed basal (CB, α2β1integrin(lo)) cells. Radiosensitivity was measured by colony-forming efficiency (CFE) and DNA damage by comet assay and DNA damage foci quantification. Immunofluorescence and flow cytometry were used to measure heterochromatin. The HDAC (histone deacetylase) inhibitor Trichostatin A was used as a radiosensitiser.Results:Stem-like cells had increased CFE post irradiation compared with the more differentiated cells (TA and CB). The SC population sustained fewer lethal double-strand breaks than either TA or CB cells, which correlated with SCs being less proliferative and having increased levels of heterochromatin. Finally, treatment with an HDAC inhibitor sensitised the SCs to radiation.Interpretation:Prostate SCs are more radioresistant than more differentiated cell populations. We suggest that the primitive cells survive radiation therapy and that pre-treatment with HDAC inhibitors may sensitise this resistant fraction.

U2 - 10.1038/bjc.2013.691

DO - 10.1038/bjc.2013.691

M3 - Article

VL - 109

SP - 3023

EP - 3033

JO - British journal of cancer

JF - British journal of cancer

SN - 0007-0920

IS - 12

ER -