Radiation-enhancement of MDA-MB-231 breast cancer cell invasion prevented by a cyclooxygenase-2 inhibitor.
Radiation-enhancement of MDA-MB-231 breast cancer cell invasion prevented by a cyclooxygenase-2 inhibitor.
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DOI：
10.1038/bjc.2011.260
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发表时间：
2011-08-09
影响因子：
8.8
通讯作者：
Bujold, R.
中科院分区：
文献类型：
--
作者：
Paquette, B.;Therriault, H.;Desmarais, G.;Wagner, R.;Royer, R.;Bujold, R.
最近的证据支持辐射可以促进癌细胞的侵袭。由于癌细胞与周围基质细胞之间的相互作用在肿瘤进展中发挥重要作用，因此我们确定对成纤维细胞的照射是否可以增强乳腺癌细胞的侵袭性。研究人员对环氧合酶 2 (COX-2)（一种经常由放疗诱导的炎症酶）的作用进行了研究。将经照射的3T3成纤维细胞铺在侵袭室的下室中，并用作未照射的人乳腺癌细胞MDA-MB-231的化学引诱剂，MDA-MB-231是雌激素受体阴性（ER（−））和雌激素受体阳性（ER（+））MCF-7细胞。通过半定量 qPCR 和蛋白质印迹测量受辐射 3T3 细胞中 COX-2 表达的刺激。使用酶谱凝胶和侵袭室评估 COX-2 的主要产物前列腺素 E2 (PGE2) 刺激基质金属蛋白酶 2 (MMP-2) 产生和癌细胞侵袭的能力。 3T3 成纤维细胞的辐射（5 Gy）增加了 COX-2 的表达，并使未辐射的 MDA-MB-231 细胞的侵袭性增强了 5.8 倍，而它们的迁移没有改变。添加 COX-2 抑制剂 NS-398 完全阻止了癌细胞侵袭的辐射增强。添加 PGE2 可以增加癌细胞侵袭以及 MDA-MB-231 细胞释放 MMP-2，这进一步支持了 COX-2 的潜在作用。辐射的这种影响取决于 1 型膜 (MT1)-MMP 的表达，这是激活 MMP-2 所必需的，但与 ER 状态无关。尽管受辐射的成纤维细胞刺激了 MDA-MB-231 ER(−) 细胞的侵袭性，但 ER(+) 细胞系 MCF-7 没有测量到增强作用。受辐射的3T3成纤维细胞诱导的乳腺癌细胞侵袭的辐射增强并不依赖于ER状态，而是依赖于MT1-MMP的表达。特定的 COX-2 抑制剂可以预防辐射的这种不利影响。
Recent evidences support that radiation can promote the invasion of cancer cells. As interactions between cancer cells and surrounding stromal cells can have an important role in tumour progression, we determined whether an irradiation to fibroblasts can enhance the invasiveness of breast cancer cells. The role of cyclooxygenase-2 (COX-2), an inflammatory enzyme frequently induced by radiotherapy, was investigated. Irradiated 3T3 fibroblasts were plated in the lower compartment of invasion chambers and used as chemoattractant for non-irradiated human breast cancer cell MDA-MB-231, which are oestrogen receptor negative (ER(−)) and the oestrogen receptor positive (ER(+)) MCF-7 cells. Stimulation of COX-2 expression in irradiated 3T3 cells was measured by a semi-quantitative qPCR and western blot. Capacity of the major product of COX-2, the prostaglandin E2 (PGE2), to stimulate the production of the matrix metalloproteinase-2 (MMP-2) and cancer cell invasion were assessed with a zymography gel and invasion chambers. Irradiation (5 Gy) of 3T3 fibroblasts increased COX-2 expression and enhanced by 5.8-fold the invasiveness of non-irradiated MDA-MB-231 cells, while their migration was not modified. Addition of the COX-2 inhibitor NS-398 completely prevented radiation-enhancement of cancer cell invasion. Further supporting the potential role of COX-2, addition of PGE2 has increased cancer cell invasion and release of MMP-2 from the MDA-MB-231 cells. This effect of radiation was dependant on the expression of membrane type 1 (MT1)–MMP, which is required to activate the MMP-2, but was not associated with the ER status. Although irradiated fibroblasts stimulated the invasiveness of MDA-MB-231 ER(−) cells, no enhancement was measured with the ER(+) cell line MCF-7. Radiation-enhancement of breast cancer cell invasion induced by irradiated 3T3 fibroblasts is not dependant on the ER status, but rather the expression of MT1–MMP. This adverse effect of radiation can be prevented by a specific COX-2 inhibitor.
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影响因子：
2.2
作者：
Nyström, J;Geladi, P;Franzen, L
通讯作者：
Franzen, L
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
3.8
作者：
Larkins TL;Nowell M;Singh S;Sanford GL
通讯作者：
Sanford GL
影响因子：
11.2
作者：
Ohuchida, K;Mizumoto, K;Tanaka, M
通讯作者：
Tanaka, M
DOI：
10.1016/s0360-3016(01)02680-3
发表时间：
2002-03-01
影响因子：
7
作者：
Chen, SC;Chen, MF;Leung, WM
通讯作者：
Leung, WM