A 3-D multicellular tumor spheroid on ultrathin matrix coated single cancer cells provides a tumor microenvironment model to study epithelial-to-mesenchymal transitions
A 3-D multicellular tumor spheroid on ultrathin matrix coated single cancer cells provides a tumor microenvironment model to study epithelial-to-mesenchymal transitions
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超薄基质包被的单个癌细胞上的 3D 多细胞肿瘤球体为研究上皮间质转化提供了肿瘤微环境模型
DOI：
10.1039/c4py01161a
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Xiaozhong Qiu
中科院分区：
文献类型：
--
作者：
Guobao Wang;Tingting ZHao;Xiaoping Song;Wen Zhong;Lei Yu;Wenxi Hua;Malcolm M. Q. Xing;Xiaozhong Qiu
我们报告了一个三维肿瘤球体模型，使用超薄基质包被的单个癌细胞研究上皮向间质转化（EMT）。采用光学显微镜、荧光成像、扫描电镜、透射电镜和zeta电位等手段对球形粒子进行了表征。然后，我们研究了EMT相关的细胞CD 47，mTOR，ERK和HIF信号转导。我们比较了EMT中（1）多细胞肿瘤球体内的细胞（3Dis），（2）从多细胞肿瘤球体迁移的细胞（3Dms）和（3）2D单层培养细胞（2Ds）。与2Ds和3Dms相比，3Dis表现出异常的细胞核，发生细胞损伤和脂滴积聚，以及更高的整合素相关蛋白表达和mTOR复合物的解离。我们检测了EMT相关因子E-和N-cadherin的表达，发现E-cadherin在2Ds中过表达，3Dis中高表达N-cadherin，3Dms中高表达E-和弱表达N-cadherin。这意味着我们的模型可以触发EMT。通过将细胞注射到异种移植模型中，我们发现2Ds从N-钙粘蛋白阴性到阳性的转变和3Ds从阳性到阴性的转变，但在3Dms中没有。2D细胞表现出比其他细胞更高的进展。这表明，体内3D肿瘤发生环境可以限制3D癌症转移的能力，但快速触发2D和3D的EMT过程。
We report a 3D tumor spheroid model to study epithelial-to-mesenchymal transition (EMT) using ultra-thin matrix coated single cancer cells. The spheroid was characterized by light microscopy, fluorescence imaging, SEM, TEM and zeta potential. We then studied EMT related cellular CD47, mTOR, ERK, and HIF signaling. We compared (1) cells inside a multicellular tumor spheroid (3Dis), (2) cells migrated from the multicellular tumor spheroid (3Dms), and (3) 2D monolayer-cultured cells (2Ds) in EMT. 3Dis exhibited an abnormal nucleus with the occurrence of cell damage and accumulation of lipid droplets, and higher expression of the integrin-associated protein and dissociation of the mTOR complex than those of 2Ds and 3Dms. We examined the expressions of E- and N-cadherin, two EMT related factors, and found over-expression of E-cadherin in 2Ds, high N-cadherin in 3Dis, and high E- and weak N-cadherin in 3Dms. This implied that our model could trigger EMT. By injecting cells into a xenograft model, we found transitions of 2Ds from N-cadherin negative to positive and transitions of 3Dis from positive to negative, but not in 3Dms. 2D cells exhibited higher progression than other cells. This suggests that the in vivo 3D tumorigenesis environment could limit the capacity of cancer metastases for 3Dis but trigger the EMT process quickly for 2Ds and 3Dms.
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影响因子：
11.2
作者：
Hu YL;DeLay M;Jahangiri A;Molinaro AM;Rose SD;Carbonell WS;Aghi MK
通讯作者：
Aghi MK
N-钙粘着蛋白在乳腺癌细胞中的外源表达会诱导细胞迁移，侵袭和转移。
影响因子：
7.8
作者：
Hazan, R B;Phillips, G R;Qiao, R F;Norton, L;Aaronson, S A
通讯作者：
Aaronson, S A
影响因子：
8
作者：
Xiang, T.;Jia, Y.;Sherris, D.;Li, S.;Wang, H.;Lu, D.;Yang, Q.
通讯作者：
Yang, Q.
影响因子：
11.2
作者：
H. Oka;H. Shiozaki;K. Kobayashi;M. Inoue;H. Tahara;Tetsurou Kobayashi;Y. Takatsuka;N. Matsuyoshi;S. Hirano;M. Takeichi;T. Mori
通讯作者：
H. Oka;H. Shiozaki;K. Kobayashi;M. Inoue;H. Tahara;Tetsurou Kobayashi;Y. Takatsuka;N. Matsuyoshi;S. Hirano;M. Takeichi;T. Mori
DOI：
10.1016/j.breastdis.2013.07.021
发表时间：
2013
期刊：
Breast Diseases: A Year Book Quarterly
影响因子：
--
作者：
Valentin V. Barsan;M. Cristofanilli;Sendurai A Mani
通讯作者：
Valentin V. Barsan;M. Cristofanilli;Sendurai A Mani