HDAC inhibitor confers radiosensitivity to prostate stem-like cells.
HDAC inhibitor confers radiosensitivity to prostate stem-like cells.
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DOI：
10.1038/bjc.2013.691
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发表时间：
2013-12-10
影响因子：
8.8
通讯作者：
Maitland, N. J.
中科院分区：
文献类型：
--
作者：
Frame, F. M.;Pellacani, D.;Collins, A. T.;Simms, M. S.;Mann, V. M.;Jones, G. D. D.;Meuth, M.;Bristow, R. G.;Maitland, N. J.
放射治疗可以是前列腺癌的有效治疗方法，但放射复发性肿瘤确实会发展。考虑到前列腺癌的异质性，我们假设原始干细胞样细胞可能构成放射抵抗部分。原代培养物来源于因前列腺癌或良性前列腺增生而接受切除术的患者。短期培养后，分选出三个细胞群，反映了前列腺上皮的层次，即干细胞样细胞（SC，α2β 1整联蛋白hi/CD 133+）、过渡扩增细胞（TA，α2β 1整联蛋白hi/CD 133 −）和定向基底细胞（CB，α2β 1整联蛋白lo）。用集落形成率（CFE）和彗星试验及DNA损伤灶定量法测定放射敏感性。用免疫荧光和流式细胞术检测异染色质。HDAC（组蛋白去乙酰化酶）抑制剂曲古抑菌素A被用作放射增敏剂。干细胞样细胞与分化程度更高的细胞（TA和CB）相比，照射后CFE增加。与TA或CB细胞相比，SC群体持续的致死性双链断裂较少，这与SC的增殖性较低和异染色质水平增加相关。最后，用HDAC抑制剂治疗使SC对辐射敏感。前列腺干细胞比更分化的细胞群更具有放射抗性。我们认为原始细胞在放射治疗中存活，并且用HDAC抑制剂预处理可能使这种抗性部分敏感。
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. 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, α2β1integrinhi/CD133+), transit-amplifying (TA, α2β1integrinhi/CD133−) and committed basal (CB, α2β1integrinlo) 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. 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. 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.
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DOI：
10.1073/pnas.0609299104
发表时间：
2007-04-24
影响因子：
11.1
作者：
Hallstrom, Taija M. Kiviharju-af;Jaamaa, Sari;Laiho, Marikki
通讯作者：
Laiho, Marikki
影响因子：
3.2
作者：
Hudson, DL;Guy, AT;Masters, JRW
通讯作者：
Masters, JRW
影响因子：
11.2
作者：
Jaamaa, Sari;af Hallstrom, Taija M.;Laiho, Marikki
通讯作者：
Laiho, Marikki
影响因子：
8
作者：
Burgess, A;Ruefli, A;Gabrielli, B
通讯作者：
Gabrielli, B
鉴定非典型畸胎组织/色肽肿瘤中CD133阳性辐射细胞。
影响因子：
3.7
作者：
Chiou, Shih-Hwa;Kao, Chung-Lan;Chen, Yi-Wei;Chien, Chien-Shu;Hung, Shih-Chieh;Lo, Jeng-Fan;Chen, Yann-Jang;Ku, Hung-Hai;Hsu, Ming-Ta;Wong, Tai-Tong
通讯作者：
Wong, Tai-Tong