Research Center, Institut Curie, F-75248 Paris, France.
Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1943-8. doi: 10.1073/pnas.1010396108. Epub 2011 Jan 18.
Cancer cells use different modes of migration, including integrin-dependent mesenchymal migration of elongated cells along elements of the 3D matrix as opposed to low-adhesion-, contraction-based amoeboid motility of rounded cells. We report that MDA-MB-231 human breast adenocarcinoma cells invade 3D Matrigel with a characteristic rounded morphology and with F-actin and myosin-IIa accumulating at the cell rear in a uropod-like structure. MDA-MB-231 cells display neither lamellipodia nor bleb extensions at the leading edge and do not require Arp2/3 complex activity for 3D invasion in Matrigel. Accumulation of phospho-MLC and blebbing activity were restricted to the uropod as reporters of actomyosin contractility, and velocimetric analysis of fluorescent beads embedded within the 3D matrix showed that pulling forces exerted to the matrix are restricted to the side and rear of cells. Inhibition of actomyosin contractility or β1 integrin function interferes with uropod formation, matrix deformation, and invasion through Matrigel. These findings support a model whereby actomyosin-based uropod contractility generates traction forces on the β1 integrin adhesion system to drive cell propulsion within the 3D matrix, with no contribution of lamellipodia extension or blebbing to movement.
癌细胞使用不同的迁移模式，包括整合素依赖性的长形细胞沿着 3D 基质的成分进行的间质迁移，而不是圆形细胞的低黏附性、基于收缩的阿米巴样运动。我们报告说，MDA-MB-231 人乳腺腺癌细胞以特征性的圆形形态侵入 3D Matrigel，在足状伪足样结构中，F-肌动蛋白和肌球蛋白-IIa 在细胞后部积累。MDA-MB-231 细胞在前缘既没有片状伪足也没有泡状延伸，并且不需要 Arp2/3 复合物活性即可在 Matrigel 中进行 3D 入侵。磷酸化肌球蛋白轻链的积累和泡状活性仅限于足状伪足，作为肌动球蛋白收缩性的报告者，并且嵌入 3D 基质中的荧光珠的速度分析表明，施加到基质的拉力仅限于细胞的侧面和后部。肌动球蛋白收缩性或 β1 整合素功能的抑制会干扰足状伪足的形成、基质变形以及通过 Matrigel 的入侵。这些发现支持了这样一种模型，即基于肌动球蛋白的足状伪足收缩性在 β1 整合素粘附系统上产生牵引力，以推动细胞在 3D 基质内推进，而片状伪足延伸或泡状延伸对运动没有贡献。
