Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo.
Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo.
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DOI：
10.1038/sj.bjc.6604288
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发表时间：
2008-04-08
影响因子：
8.8
通讯作者：
Jarrard, D. F.
中科院分区：
文献类型：
--
作者：
Ewald, J. A.;Desotelle, J. A.;Almassi, N.;Jarrard, D. F.
衰老是一种由 DNA 损伤剂和其他亚致死应激源诱导的独特细胞反应，可能为癌症治疗提供新的益处。然而，在衰老模型中，发现衰老的成纤维细胞会刺激共培养细胞的增殖。为了解决使用化疗诱导癌细胞衰老是否会产生类似的效果，我们使用了 GFP 标记的前列腺癌细胞系，并在体外和体内监测了它们在增殖或阿霉素诱导的衰老癌细胞存在下的增殖情况。在这里，我们发现衰老癌细胞的存在通过旁分泌信号因子增加了体外共培养细胞的增殖，但这种增殖效应明显低于衰老成纤维细胞的增殖效应。在体内，衰老癌细胞未能增加裸鼠中 LNCaP 和 DU145 异种移植物的建立、生长或增殖。衰老细胞在肿瘤中持续存在长达 5 周。我们的结果表明，尽管药物诱导的衰老癌细胞在体外刺激旁观者细胞的增殖，但这并没有显着改变体内肿瘤的生长。结合临床观察，这些数据表明衰老癌细胞的增殖旁观者效应可以忽略不计，并支持衰老诱导疗法的进一步发展。
Senescence is a distinct cellular response induced by DNA-damaging agents and other sublethal stressors and may provide novel benefits in cancer therapy. However, in an ageing model, senescent fibroblasts were found to stimulate the proliferation of cocultured cells. To address whether senescence induction in cancer cells using chemotherapy induces similar effects, we used GFP-labelled prostate cancer cell lines and monitored their proliferation in the presence of proliferating or doxorubicin-induced senescent cancer cells in vitro and in vivo. Here, we show that the presence of senescent cancer cells increased the proliferation of cocultured cells in vitro through paracrine signalling factors, but this proliferative effect was significantly less than that seen with senescent fibroblasts. In vivo, senescent cancer cells failed to increase the establishment, growth or proliferation of LNCaP and DU145 xenografts in nude mice. Senescent cells persisted as long as 5 weeks in tumours. Our results demonstrate that although drug-induced senescent cancer cells stimulate the proliferation of bystander cells in vitro, this does not significantly alter the growth of tumours in vivo. Coupled with clinical observations, these data suggest that the proliferative bystander effects of senescent cancer cells are negligible and support the further development of senescence induction as therapy.
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影响因子：
11.2
作者：
Bavik, C;Coleman, I;Nelson, PS
通讯作者：
Nelson, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
11.2
作者：
Petti, Carlotta;Molla, Alessandra;Sensi, Marialuisa
通讯作者：
Sensi, Marialuisa
影响因子：
2.1
作者：
Choi, J;Shendrik, I;Benson, MC
通讯作者：
Benson, MC
DOI：
10.1073/pnas.211053698
发表时间：
2001-10-09
影响因子：
11.1
作者：
Krtolica, A;Parrinello, S;Campisi, J
通讯作者：
Campisi, J