Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment.
Organoids with cancer stem cell-like properties secrete exosomes and HSP90 in a 3D nanoenvironment.
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DOI：
10.1371/journal.pone.0191109
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Calderwood SK
中科院分区：
文献类型：
--
作者：
Eguchi T;Sogawa C;Okusha Y;Uchibe K;Iinuma R;Ono K;Nakano K;Murakami J;Itoh M;Arai K;Fujiwara T;Namba Y;Murata Y;Ohyama K;Shimomura M;Okamura H;Takigawa M;Nakatsura T;Kozaki KI;Okamoto K;Calderwood SK
形成肿瘤球体和球体等细胞聚集的能力已被用作恶性肿瘤细胞，特别是癌症干细胞(CSC)的形态标志。然而，对癌细胞形成的细胞聚集的类型的共同定义还没有得到。我们研究了在三维形态增强纳米培养板(NCP)上培养的67个细胞株的形态，并对形成的细胞聚集体的类型进行了分类。在67个细胞系中，49个细胞系呈球状或椭圆形，8个细胞系呈葡萄状聚集(GLA)，8个细胞系呈其他类型聚集，3个细胞系呈单层片状。在这8个细胞系中，有7个GLA形成细胞系来源于腺癌。神经内分泌腺癌细胞系PC-3在NCP上形成具有导管结构的不对称GLA，并在免疫低下小鼠体内形成迅速生长的不对称肿瘤，转移到淋巴结。相反，另一种腺癌细胞系DU-145在体外形成球形肿瘤，在体内形成球形肿瘤，直到移植后第50天才转移到淋巴结。在3D纳米环境和特定的干细胞培养液中培养，神经内分泌腺癌细胞能够在体外形成缓慢生长的大有机物，表达多种干细胞标志物、神经内分泌标志物、细胞间黏附分子和癌基因。相比之下，更常用的2D含血清环境减少了细胞间的黏附，诱导了间充质转化，促进了细胞的快速生长。此外，3D茎纳米环境促进了神经内分泌器官分泌HSP90和EpCAM-exosome，这是CSC表型的标志。这些发现表明，基于NCP的3D环境使细胞能够形成多潜能的干细胞肿瘤样体，并在形态和基因表达水平上更准确地模拟体内肿瘤状态。
Ability to form cellular aggregations such as tumorspheres and spheroids have been used as a morphological marker of malignant cancer cells and in particular cancer stem cells (CSC). However, the common definition of the types of cellular aggregation formed by cancer cells has not been available. We examined morphologies of 67 cell lines cultured on three dimensional morphology enhancing NanoCulture Plates (NCP) and classified the types of cellular aggregates that form. Among the 67 cell lines, 49 cell lines formed spheres or spheroids, 8 cell lines formed grape-like aggregation (GLA), 8 cell lines formed other types of aggregation, and 3 cell lines formed monolayer sheets. Seven GLA-forming cell lines were derived from adenocarcinoma among the 8 lines. A neuroendocrine adenocarcinoma cell line PC-3 formed asymmetric GLA with ductal structures on the NCPs and rapidly growing asymmetric tumors that metastasized to lymph nodes in immunocompromised mice. In contrast, another adenocarcinoma cell line DU-145 formed spheroids in vitro and spheroid-like tumors in vivo that did not metastasize to lymph nodes until day 50 after transplantation. Culture in the 3D nanoenvironment and in a defined stem cell medium enabled the neuroendocrine adenocarcinoma cells to form slowly growing large organoids that expressed multiple stem cell markers, neuroendocrine markers, intercellular adhesion molecules, and oncogenes in vitro. In contrast, the more commonly used 2D serum-contained environment reduced intercellular adhesion and induced mesenchymal transition and promoted rapid growth of the cells. In addition, the 3D stemness nanoenvironment promoted secretion of HSP90 and EpCAM-exosomes, a marker of CSC phenotype, from the neuroendocrine organoids. These findings indicate that the NCP-based 3D environment enables cells to form stem cell tumoroids with multipotency and model more accurately the in vivo tumor status at the levels of morphology and gene expression.
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影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
3.7
作者：
Chou SD;Prince T;Gong J;Calderwood SK
通讯作者：
Calderwood SK
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.7
作者：
Arai K;Eguchi T;Rahman MM;Sakamoto R;Masuda N;Nakatsura T;Calderwood SK;Kozaki K;Itoh M
通讯作者：
Itoh M
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ