Do cancer cells have distinct adhesions in 3D collagen matrices and in vivo?
Do cancer cells have distinct adhesions in 3D collagen matrices and in vivo?
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DOI：
10.1016/j.ejcb.2012.07.005
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发表时间：
2012-11-01
影响因子：
6.6
通讯作者：
Vignjevic, Danijela M.
中科院分区：
文献类型：
--
作者：
Geraldo, Sara;Simon, Anthony;Vignjevic, Danijela M.
在转移过程中，癌细胞突破基底膜并迁移通过主要由胶原I纤维网络组成的基质。细胞在2D上的迁移是由细胞膜的突出引发的，随后是将肌动蛋白细胞骨架连接到细胞外基质（ECM）的粘附的形成。然后，细胞通过在其前部的粘连上施加牵引力并通过在后部的粘连分解而向前移动。在2D中，只有迁移细胞的腹侧表面与ECM接触，在那里组装细胞-基质粘附。在3D矩阵中，即使迁移细胞的整个表面可用于与ECM相互作用，但不清楚离散的粘附结构是否实际存在。使用高分辨率共聚焦显微镜，我们成像的内源性粘附体蛋白在三种不同的癌细胞类型嵌入在非胃蛋白酶化的胶原蛋白I型，聚合在一个缓慢的速度，以允许形成一个网络，类似于组织的EMC在体内观察到。在细胞突起中检测到了骨胶原蛋白聚集体，经常与胶原纤维共定位，这意味着它们对应于3D中的粘附结构。随着与基底底部的距离增加，粘附聚集体变得更小，并且在一些细胞系中几乎检测不到。使用活体成像，我们在这里显示，为第一次，在体内存在的粘附体蛋白聚集体。这些聚集体与3D胶原基质中发现的聚集体具有相似性。仍有待确定的是，在3D和体内组装的粘连是否与2D中充分描述的粘连具有功能相似性。这将为理解细胞在更多生理环境中的迁移迈出重要一步。(C)2012 Elsevier GmbH. All rights reserved.
uring metastasis, cancer cells breach the basement membrane and migrate through the stroma mostly composed of a network of collagen I fibers. Cell migration on 2D is initiated by protrusion of the cell membrane followed by formation of adhesions that link the actin cytoskeleton to the extracellular matrix (ECM). Cells then move forwards by exerting traction forces on the adhesions at its front and by disassembling adhesions at the rear. In 2D, only the ventral surface of a migrating cell is in contact with the ECM, where cell-matrix adhesions are assembled. In 3D matrices, even though the whole surface of a migrating cell is available for interacting with the ECM, it is unclear whether discrete adhesion structures actually exist. Using high-resolution confocal microscopy we imaged the endogenous adhesome proteins in three different cancer cell types embedded in non-pepsinized collagen type I, polymerized at a slow rate, to allow the formation of a network that resembles the organization of EMC observed in vivo. Vinculin aggregates were detected in the cellular protrusions, frequently colocalizing with collagen fibers, implying they correspond to adhesion structures in 3D. As the distance from the substrate bottom increases, adhesion aggregates become smaller and almost undetectable in some cell lines. Using intravital imaging we show here, for the first time, the existence of adhesome proteins aggregates in vivo. These aggregates share similarities with the ones found in 3D collagen matrices. It still remains to be determined if adhesions assembled in 3D and in vivo share functional similarities to the well-described adhesions in 2D. This will provide a major step forward in understanding cell migration in more physiological environments. (C) 2012 Elsevier GmbH. All rights reserved.