Transforming growth factor-β signalling controls human breast cancer metastasis in a zebrafish xenograft model.
Transforming growth factor-β signalling controls human breast cancer metastasis in a zebrafish xenograft model.
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DOI：
10.1186/bcr3573
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发表时间：
2013-11-07
期刊：
影响因子：
--
通讯作者：
ten Dijke P
中科院分区：
文献类型：
--
作者：
Drabsch Y;He S;Zhang L;Snaar-Jagalska BE;ten Dijke P
已知转化生长因子β (TGF-β)信号通路控制人类乳腺癌的侵袭和转移。我们证明，斑马鱼异种移植试验是一种强大而可靠的动物模型，用于检查人类乳腺肿瘤细胞中TGF-β信号的药理调节剂和遗传扰动的作用。我们将癌细胞注入胚胎循环（居维叶管），观察其向无血管的胶原尾的侵袭和转移。TGF-β信号通路的各个方面被化学抑制、小干扰RNA （siRNA）或小发夹RNA （shRNA）阻断。采用荧光显微镜进行分析。根据体外和体内小鼠研究，不同恶性程度的乳腺癌细胞在胚胎斑马鱼模型中表现出侵袭性和转移性，这与它们在小鼠模型中的不同致瘤性很好地相关。有趣的是，MCF10A M2和M4细胞侵入尾鳍造血组织，可见为细胞簇，而MDA MB 231细胞侵入尾鳍，可见为单个细胞。TGF-β受体激酶抑制剂或肿瘤特异性Smad4敲除的药理抑制干扰了斑马鱼异种移植模型的侵袭和转移，并与我们在小鼠转移模型中使用这些细胞获得的结果非常相似。抑制TGF-β在乳腺癌细胞中诱导的基质金属蛋白酶，阻断乳腺癌细胞的侵袭和转移。斑马鱼-胚胎乳腺癌异种移植模型适用于了解机制，筛选和开发抗tgf -β药物，及时、高性价比地治疗转移性乳腺癌。
The transforming growth factor beta (TGF-β) signalling pathway is known to control human breast cancer invasion and metastasis. We demonstrate that the zebrafish xenograft assay is a robust and dependable animal model for examining the role of pharmacological modulators and genetic perturbation of TGF-β signalling in human breast tumour cells. We injected cancer cells into the embryonic circulation (duct of cuvier) and examined their invasion and metastasis into the avascular collagenous tail. Various aspects of the TGF-β signalling pathway were blocked by chemical inhibition, small interfering RNA (siRNA), or small hairpin RNA (shRNA). Analysis was conducted using fluorescent microscopy. Breast cancer cells with different levels of malignancy, according to in vitro and in vivo mouse studies, demonstrated invasive and metastatic properties within the embryonic zebrafish model that nicely correlated with their differential tumourigenicity in mouse models. Interestingly, MCF10A M2 and M4 cells invaded into the caudal hematopoietic tissue and were visible as a cluster of cells, whereas MDA MB 231 cells invaded into the tail fin and were visible as individual cells. Pharmacological inhibition with TGF-β receptor kinase inhibitors or tumour specific Smad4 knockdown disturbed invasion and metastasis in the zebrafish xenograft model and closely mimicked the results we obtained with these cells in a mouse metastasis model. Inhibition of matrix metallo proteinases, which are induced by TGF-β in breast cancer cells, blocked invasion and metastasis of breast cancer cells. The zebrafish-embryonic breast cancer xenograft model is applicable for the mechanistic understanding, screening and development of anti-TGF-β drugs for the treatment of metastatic breast cancer in a timely and cost-effective manner.
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影响因子：
4.8
作者：
Kohli, G;Hu, SQ;Peng, C
通讯作者：
Peng, C
影响因子：
11.2
作者：
Deckers, M;van Dinther, M;ten Dijke, P
通讯作者：
ten Dijke, P
影响因子：
9.8
作者：
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自动化的全动物生物成像分析用于人类癌症传播。
影响因子：
3.7
作者：
Ghotra VP;He S;de Bont H;van der Ent W;Spaink HP;van de Water B;Snaar-Jagalska BE;Danen EH
通讯作者：
Danen EH
影响因子：
45.3
作者：
Goessling, Wolfram;North, Trista E.;Zon, Leonard I.
通讯作者：
Zon, Leonard I.