Integrins, cell matrix interactions and cell migration strategies:: Fundamental differences in leukocytes and tumor cells
Integrins, cell matrix interactions and cell migration strategies:: Fundamental differences in leukocytes and tumor cells
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DOI：
10.3109/15419069809004478
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Zänker, KS
中科院分区：
文献类型：
--
作者：
Friedl, P;Bröcker, EB;Zänker, KS
决定不同细胞类型迁移的原理可能是由于它们的来源、大小和形状、粘附受体的功能以及环境因素（包括细胞外基质）的差异造成的。在三维胶原蛋白晶格中迁移的极化白细胞（T 淋巴细胞和树突状细胞）较小，形成高度动态的前缘和尾足，而侵袭性黑色素瘤细胞较大、高度极化且动态较差。与白细胞相反，肿瘤细胞可能另外形成迁移细胞簇，维持强烈的细胞间相互作用和簇极性。白细胞表现出由基质纤维强烈引导的速度导向、振荡和方向不可预测的路径轮廓，而黑色素瘤细胞和迁移细胞簇表现出缓慢但高度定向的迁移。白细胞在完全没有组织重塑的情况下与胶原纤维形成短暂的相互作用，而黑色素瘤细胞和肿瘤细胞簇则通过附着部位的深度拉力、分离时有限的纤维破坏以及细胞表面决定因素的脱落来重组基质。使用阻断性抗整合素抗体，肿瘤细胞迁移和迁移相关的基质重组被证明依赖于β1整合素介导的粘附，而迁移T细胞不能被一组抗β1-、β2-、β3-和α-整合素抗体单独或组合抑制。因此，迁移的黑色素瘤细胞利用与胶原纤维接触处的细胞骨架成分共簇的整联蛋白的粘着斑。然而，T 细胞缺乏典型的粘着斑，将 β1 整合素重新分配到尾足，并将粘着斑激酶重新分配到前缘。总之，黑色素瘤细胞采用的粘附依赖性和重组迁移类型可能与白细胞使用的很大程度上不依赖于整合素和非重组迁移策略不同。
The principles determining the migration of different cell types may result from their differences in origin, size and shape, function of adhesion receptors, and environmental factors, including the extracellular matrix. Polarized leukocytes (T lymphocytes and dendritic cells) migrating in three-dimensional collagen lattices are small developing a highly dynamic leading edge and a trailing uropod, whereas invasive melanoma cells are larger, highly polarized and less dynamic. In contrast to leukocytes, tumor cells may additionally develop migrating cell clusters maintaining intense cell-cell interaction and cluster polarity. Leukocytes show a speed-oriented, oscillating and directionally unpredictable path profile strongly guided by matrix fibers, while melanoma cells and migrating cell clusters exhibit slow yet highly directional migration. Whereas leukocytes form short-lived interactions with collagen fibers in complete absence of tissue remodeling, melanoma cells and neoplastic cell clusters reorganize the matrix via profound pulling at attachment sites, limited fiber disruption upon detachment, and the shedding of cell surface determinants. Using blocking anti-integrin antibodies, tumor cell migration and migration-associated matrix reorganization were shown to be dependent on beta 1 integrin-mediated adhesion, whereas migrating T cells cannot be inhibited by a panel of anti-beta 1-, beta 2-, beta 3-, and alpha-integrin antibodies, either alone or in combination. Consequently, migrating melanoma cells use focal adhesions of integrins coclustered with cytoskeletal components at contacts with collagen fibers. T cells, however, lack typical focal adhesions, redistribute beta 1 integrins to the uropod and the focal adhesion kinase to the leading edge. In conclusion, an adhesion-dependent and reorganizing migration type employed by melanoma cells may be distinct from largely integrin-independent and non-reorganizing migration strategies used by leukocytes.