The interplay of cell-cell and cell-matrix interactions in the invasive properties of brain tumors
The interplay of cell-cell and cell-matrix interactions in the invasive properties of brain tumors
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DOI：
10.1529/biophysj.105.077834
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发表时间：
2006-10-01
影响因子：
3.4
通讯作者：
Forgacs, Gabor
中科院分区：
文献类型：
--
作者：
Hegedus, Balazs;Marga, Francoise;Forgacs, Gabor
组织凝聚力的损害和细胞外基质的重组是向侵袭性细胞表型发展过程中的关键事件。我们研究了九种脑肿瘤细胞系在三维胶原凝胶中的体外侵袭模式。细胞-细胞和细胞-基质的相互作用进行了定量和相关的特定分子的表达水平：N-钙粘蛋白，基质金属蛋白酶，及其抑制剂。图案演变作为时间和胶原蛋白浓度的函数进行了研究。低金属蛋白酶表达或高组织凝聚力的细胞表现出有限的侵袭潜力。较高的金属蛋白酶表达和中等的组织凝聚力导致周围区域的高细胞区的配置，大部分没有细胞和消化胶原蛋白，类似于手术切除的恶性星形细胞瘤标本中的pseudopalisades。在物理方面，这些配置出现作为细胞之间的竞争和细胞基质之间的相互作用的结果。我们的研究结果提出了表征、控制或设计细胞迁移模式的具体方法，并暗示了生物物理和生物分子因素之间的相互作用在表征侵袭性细胞行为以及更一般地在上皮-间充质转变中的重要性。
Impairment of tissue cohesion and the reorganization of the extracellular matrix are crucial events during the progression toward invasive cell phenotype. We studied the in vitro invasion patterns of nine brain tumor cell lines in three-dimensional collagen gels. Cell-cell and cell-matrix interactions were quantified and correlated with the expression level of specific molecules: N-cadherin, matrix metalloproteinases, and their inhibitor. Pattern evolution was studied as a function of time and collagen concentration. Cells with low metalloproteinase expression or high tissue cohesion showed limited invasive potential. Higher metalloproteinase expression and intermediate tissue cohesion resulted in configurations with hypercellular zones surrounding regions mostly devoid of cells and with digested collagen, akin to pseudopalisades in surgically removed malignant astrocytoma specimens. In physical terms, these configurations arise as the result of competition between cell-cell and cell-matrix interactions. Our findings suggest specific ways to characterize, control, or engineer cell migratory patterns and hint at the importance of the interplay between biophysical and biomolecular factors in the characterization of invasive cell behavior and, more generally, in epithelial-mesenchymal transitions.