3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry.
3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry.
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DOI：
10.1038/s41467-017-01556-7
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发表时间：
2017-11-21
影响因子：
16.6
通讯作者：
Fraley SI
中科院分区：
文献类型：
--
作者：
Velez DO;Tsui B;Goshia T;Chute CL;Han A;Carter H;Fraley SI
肿瘤微环境中胶原蛋白的拓扑结构与调节癌细胞迁移有关，并独立预测转移的进展。在这里，我们表明，胶原蛋白基质具有小孔和短纤维，但不是Matrigel，触发保守的转录反应和随后的运动开关在癌细胞中导致形成多细胞网络结构。这种反应不是由缺氧、基质硬度或基质体积密度介导的，而是由基质结构诱导的β1-整合素上调介导的。与网络形成相关的转录模块富含迁移和血管生成相关基因，这些基因可预测9种不同肿瘤类型患者数据中的生存率。在显示血管生成拟态（VM）表型的患者肿瘤切片中发现了该基因模块在蛋白质水平上的证据。我们的研究结果将胶原诱导的迁移程序与VM联系起来，并表明这一过程可能与人类实体癌的转移进展广泛相关。细胞外基质在推动癌症发展中起着核心作用。在这里，作者使用体外方法表明，限制胶原蛋白结构诱导快速和持久的细胞迁移，并形成与患者肿瘤中观察到的血管拟态相关的多细胞网络结构。
The topographical organization of collagen within the tumor microenvironment has been implicated in modulating cancer cell migration and independently predicts progression to metastasis. Here, we show that collagen matrices with small pores and short fibers, but not Matrigel, trigger a conserved transcriptional response and subsequent motility switch in cancer cells resulting in the formation of multicellular network structures. The response is not mediated by hypoxia, matrix stiffness, or bulk matrix density, but rather by matrix architecture-induced β1-integrin upregulation. The transcriptional module associated with network formation is enriched for migration and vasculogenesis-associated genes that predict survival in patient data across nine distinct tumor types. Evidence of this gene module at the protein level is found in patient tumor slices displaying a vasculogenic mimicry (VM) phenotype. Our findings link a collagen-induced migration program to VM and suggest that this process may be broadly relevant to metastatic progression in solid human cancers. Extracellular matrix plays a central role in driving cancer development. Here the authors using an in vitro approach show that confining collagen architectures induce fast and persistent cell migration and the formation of multicellular network structures linked to vascular mimicry observed in tumours from patients.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
6
作者：
Conklin, Matthew W.;Eickhoff, Jens C.;Keely, Patricia J.
通讯作者：
Keely, Patricia J.
影响因子：
4
作者：
Castro-Sanchez, Luis;Soto-Guzman, Adriana;Perez Salazar, Eduardo
通讯作者：
Perez Salazar, Eduardo
粘着斑蛋白在三维细胞运动中的独特作用。
影响因子：
21.3
作者：
Fraley, Stephanie I.;Feng, Yunfeng;Krishnamurthy, Ranjini;Kim, Dong-Hwee;Celedon, Alfredo;Longmore, Gregory D.;Wirtz, Denis
通讯作者：
Wirtz, Denis
影响因子：
--
作者：
Brinkerhoff, CJ;Linderman, JJ
通讯作者：
Linderman, JJ