Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties.
Endothelial cells provide a notch-dependent pro-tumoral niche for enhancing breast cancer survival, stemness and pro-metastatic properties.
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DOI：
10.1371/journal.pone.0112424
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rafii A
中科院分区：
文献类型：
--
作者：
Ghiabi P;Jiang J;Pasquier J;Maleki M;Abu-Kaoud N;Rafii S;Rafii A
由于肿瘤的复杂性和异质性，治疗转移具有挑战性。这种复杂性部分与肿瘤与其微环境之间的串扰有关。内皮细胞-肿瘤血管系统的构建块-已被证明在癌症进展中具有比血管生成和供应氧气和营养物更多的作用。在这里，我们展示了内皮细胞在支持乳腺癌生长和扩散中的替代作用，而不依赖于它们的血管功能。使用内皮细胞和乳腺癌细胞系MDA-MB 231和MCF-7，我们开发了共培养系统，通过体外和体内方法研究肿瘤内皮对乳腺肿瘤发展的影响。我们的结果表明，内皮细胞赋予肿瘤细胞在完全饥饿下的生存优势，并在肿瘤细胞中富集了CD 44 HighCD 24 Low/-干细胞群。此外，内皮细胞增强了乳腺癌细胞的促转移潜力。体外和体内结果一致地证实了内皮锯齿蛋白1通过缺口激活促进乳腺肿瘤的作用。在这里，我们提出了内皮细胞在增强乳腺癌的进展，干性，并通过灌注独立的方式促转移性状的作用。我们的发现可能有助于开发新的治疗方法。
Treating metastasis has been challenging due to tumors complexity and heterogeneity. This complexity is partly related to the crosstalk between tumor and its microenvironment. Endothelial cells -the building blocks of tumor vasculature- have been shown to have additional roles in cancer progression than angiogenesis and supplying oxygen and nutrients. Here, we show an alternative role for endothelial cells in supporting breast cancer growth and spreading independent of their vascular functions. Using endothelial cells and breast cancer cell lines MDA-MB231 and MCF-7, we developed co-culture systems to study the influence of tumor endothelium on breast tumor development by both in vitro and in vivo approaches. Our results demonstrated that endothelial cells conferred survival advantage to tumor cells under complete starvation and enriched the CD44HighCD24Low/- stem cell population in tumor cells. Moreover, endothelial cells enhanced the pro-metastatic potential of breast cancer cells. The in vitro and in vivo results concordantly confirmed a role for endothelial Jagged1 to promote breast tumor through notch activation. Here, we propose a role for endothelial cells in enhancing breast cancer progression, stemness, and pro-metastatic traits through a perfusion-independent manner. Our findings may be beneficial in developing novel therapeutic approaches.
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影响因子：
23.9
作者：
Butler JM;Nolan DJ;Vertes EL;Varnum-Finney B;Kobayashi H;Hooper AT;Seandel M;Shido K;White IA;Kobayashi M;Witte L;May C;Shawber C;Kimura Y;Kitajewski J;Rosenwaks Z;Bernstein ID;Rafii S
通讯作者：
Rafii S
DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
56.9
作者：
Lammert, E;Cleaver, O;Melton, D
通讯作者：
Melton, D
影响因子：
23.9
作者：
Bouras, Toula;Pal, Bhupinder;Visvader, Jane E.
通讯作者：
Visvader, Jane E.