Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607, USA.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27607, USA.
J Cell Sci. 2019 Sep 9;132(17):jcs231563. doi: 10.1242/jcs.231563.
Metastasis accounts for the majority of all cancer deaths, yet the process remains poorly understood. A pivotal step in the metastasis process is the exiting of tumor cells from the circulation, a process known as extravasation. However, it is unclear how tumor cells extravasate and whether multicellular clusters of tumor cells possess the ability to exit as a whole or must first disassociate. In this study, we use zebrafish and mouse models to elucidate the mechanism tumor cells use to extravasate. We found that circulating tumor cells exit the circulation using the recently identified extravasation mechanism, angiopellosis, and do so as both clusters and individual cells. We further show that when melanoma and cervical cancer cells utilize this extravasation method to exit as clusters, they exhibit an increased ability to form tumors at distant sites through the expression of unique genetic profiles. Collectively, we present a new model for tumor cell extravasation of both individual and multicellular circulating tumor cells.This article has an associated First Person interview with the first author of the paper.
转移是癌症死亡的主要原因，但这一过程仍未被充分理解。转移过程中的一个关键步骤是肿瘤细胞从循环系统中逸出，这个过程被称为血管外渗。然而，目前尚不清楚肿瘤细胞是如何逸出的，以及多细胞肿瘤细胞簇是否具有整体逸出的能力，还是必须首先解体。在这项研究中，我们使用斑马鱼和小鼠模型来阐明肿瘤细胞逸出的机制。我们发现，循环中的肿瘤细胞使用最近发现的血管外渗机制——血管外膜化，以集群和单个细胞的形式离开循环。我们进一步表明，当黑色素瘤和宫颈癌细胞利用这种血管外渗方法以集群的形式离开时，它们通过表达独特的遗传特征，增加了在远处形成肿瘤的能力。总的来说，我们提出了一个新的模型，用于个体和多细胞循环肿瘤细胞的血管外渗。这篇文章有一个与该论文第一作者的第一人称访谈。
