Faculty of Physics and Earth Science, Institute for Experimental Physics I, Soft Matter Physics Division, University of Leipzig, 04103 Leipzig, Germany.
J Cell Sci. 2011 Feb 1;124(Pt 3):369-83. doi: 10.1242/jcs.071985. Epub 2011 Jan 11.
Cell migration through connective tissue, or cell invasion, is a fundamental biomechanical process during metastasis formation. Cell invasion usually requires cell adhesion to the extracellular matrix through integrins. In some tumors, increased integrin expression is associated with increased malignancy and metastasis formation. Here, we have studied the invasion of cancer cells with different α5β1 integrin expression levels into loose and dense 3D collagen fiber matrices. Using a cell sorter, we isolated from parental MDA-MB-231 breast cancer cells two subcell lines expressing either high or low amounts of α5β1 integrins (α5β1(high) or α5β1(low) cells, respectively). α5β1(high) cells showed threefold increased cell invasiveness compared to α5β1(low) cells. Similar results were obtained for 786-O kidney and T24 bladder carcinoma cells, and cells in which the α5 integrin subunit was knocked down using specific siRNA. Knockdown of the collagen receptor integrin subunit α2 also reduced invasiveness, but to a lesser degree than knockdown of integrin subunit α5. Fourier transform traction microscopy revealed that the α5β1(high) cells generated sevenfold greater contractile forces than α5β1(low) cells. Cell invasiveness was reduced after addition of the myosin light chain kinase inhibitor ML-7 in α5β1(high) cells, but not in α5β1(low) cells, suggesting that α5β1 integrins enhance cell invasion through enhanced transmission and generation of contractile forces.
细胞通过结缔组织的迁移，或细胞侵袭，是转移形成过程中的一个基本生物力学过程。细胞侵袭通常需要细胞通过整合素与细胞外基质黏附。在一些肿瘤中，整合素表达的增加与恶性程度的增加和转移的形成有关。在这里，我们研究了不同α5β1 整合素表达水平的癌细胞对疏松和致密 3D 胶原纤维基质的侵袭。使用细胞分选器，我们从亲本 MDA-MB-231 乳腺癌细胞中分离出两种亚细胞系，分别表达高或低水平的α5β1 整合素（分别为α5β1（高）或α5β1（低）细胞）。与α5β1（低）细胞相比，α5β1（高）细胞的细胞侵袭性增加了三倍。同样的结果也在 786-O 肾癌细胞和 T24 膀胱癌细胞以及使用特异性 siRNA 敲低α5 整合素亚基的细胞中得到了验证。敲低胶原受体整合素亚基α2也降低了侵袭性，但程度低于敲低整合素亚基α5。傅里叶变换牵引显微镜显示，α5β1（高）细胞产生的收缩力比α5β1（低）细胞大七倍。在 α5β1（高）细胞中加入肌球蛋白轻链激酶抑制剂 ML-7 后，细胞侵袭性降低，但在α5β1（低）细胞中没有，这表明α5β1 整合素通过增强收缩力的传递和产生来增强细胞侵袭性。
