A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment.
A cancer stem cell model as the point of origin of cancer-associated fibroblasts in tumor microenvironment.
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DOI：
10.1038/s41598-017-07144-5
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发表时间：
2017-07-28
影响因子：
4.6
通讯作者：
Seno M
中科院分区：
文献类型：
--
作者：
Nair N;Calle AS;Zahra MH;Prieto-Vila M;Oo AKK;Hurley L;Vaidyanath A;Seno A;Masuda J;Iwasaki Y;Tanaka H;Kasai T;Seno M
癌症相关成纤维细胞（CAF）是肿瘤微环境基质区室中最突出的细胞类型之一。CAF支持癌症进展的多个方面，包括肿瘤起始、侵袭和转移。基质微环境的异质性归因于该隔室中的细胞来源于多个来源。本研究提供了第一个证据，即癌症干细胞（CSC）是肿瘤生态位中CAF的关键来源之一。我们通过用来自乳腺癌细胞系的条件培养基处理小鼠诱导多能干细胞来产生CSC样细胞。所得到的细胞群表达CSC和多能性标志物，并且形成球体的CSC样细胞在裸鼠中形成皮下肿瘤。有趣的是，这些CSC样细胞总是形成被肌纤维母细胞样细胞包围的异质群体。基于这一观察结果，我们假设CSC可能是支持肿瘤维持和存活的CAF的来源。为了解决这一假设，我们诱导分化的球体和纯化的肌成纤维细胞样细胞。所得到的细胞表现出CAF样表型，表明它们已分化成支持CSC自我更新的细胞亚群。这些发现提供了新的见解，各种微环境因素和CAFs在CSC利基之间的动态相互作用。
Cancer-associated fibroblasts (CAFs) are one of the most prominent cell types in the stromal compartment of the tumor microenvironment. CAFs support multiple aspects of cancer progression, including tumor initiation, invasion, and metastasis. The heterogeneous nature of the stromal microenvironment is attributed to the multiple sources from which the cells in this compartment originate. The present study provides the first evidence that cancer stem cells (CSCs) are one of the key sources of CAFs in the tumor niche. We generated CSC-like cells by treating mouse induced pluripotent stem cells with conditioned medium from breast cancer cell lines. The resulting cell population expressed both CSC and pluripotency markers, and the sphere-forming CSC-like cells formed subcutaneous tumors in nude mice. Intriguingly, these CSC-like cells always formed heterogeneous populations surrounded by myofibroblast-like cells. Based on this observation, we hypothesized that CSCs could be the source of the CAFs that support tumor maintenance and survival. To address this hypothesis, we induced the differentiation of spheres and purified the myofibroblast-like cells. The resulting cells exhibited a CAF-like phenotype, suggesting that they had differentiated into the subpopulations of cells that support CSC self-renewal. These findings provide novel insights into the dynamic interplay between various microenvironmental factors and CAFs in the CSC niche.
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DOI：
10.3791/52801
发表时间：
2015-06-20
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Lonardo E;Cioffi M;Sancho P;Crusz S;Heeschen C
通讯作者：
Heeschen C
影响因子：
6.1
作者：
Chen, Hsin-Fu;Chuang, Ching-Yu;Kuo, Hung-Chih
通讯作者：
Kuo, Hung-Chih
影响因子：
11.5
作者：
Herrera, Mercedes;Islam, Abul B. M. M. K.;Pena, Cristina
通讯作者：
Pena, Cristina
影响因子：
8
作者：
Jeter, C. R.;Liu, B.;Liu, X.;Chen, X.;Liu, C.;Calhoun-Davis, T.;Repass, J.;Zaehres, H.;Shen, J. J.;Tang, D. G.
通讯作者：
Tang, D. G.
癌症相关成纤维细胞通过旁分泌信号调节肺癌干细胞的可塑性
影响因子：
16.6
作者：
Chen, Wan-Jiun;Ho, Chao-Chi;Yang, Pan-Chyr
通讯作者：
Yang, Pan-Chyr