Role of E-cadherin in the response of tumor cell aggregates to lymphatic, venous and arterial flow: measurement of cell-cell adhesion strength.
Role of E-cadherin in the response of tumor cell aggregates to lymphatic, venous and arterial flow: measurement of cell-cell adhesion strength.
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发表时间：
1995-05
影响因子：
4
通讯作者：
Stephen W. Byers;Connie L. Sommers;B. Hoxter;A. Mercurio;Aydin Tozeren
中科院分区：
文献类型：
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作者：
Stephen W. Byers;Connie L. Sommers;B. Hoxter;A. Mercurio;Aydin Tozeren
钙依赖细胞-细胞黏附分子E-钙粘附素的表达或功能缺陷在浸润性、转移性癌中很常见。在本研究中，研究了乳腺上皮细胞、乳腺癌细胞和结肠癌细胞聚集体对平行平板流道中层流所施加的力的响应。尽管E-钙粘附素阴性的肿瘤细胞在有钙存在的情况下形成细胞聚集体，但这些细胞聚集体明显比E-钙粘附素阳性的细胞聚集体更有可能在低剪切力(如淋巴管或小静脉中发现的剪切力(100dyn/cm2))下解体。只有当表达的蛋白质适当地连接到细胞骨架时，E-钙粘素阴性的癌细胞才会显示出粘附力的大幅增加。这些结果表明，E-钙粘素阴性的肿瘤细胞，即存在黏附分子但与细胞骨架连接效率低下的细胞，比E-钙粘附素阳性细胞更有可能在低剪切力(如淋巴管或小静脉中发现的剪切力)下从肿瘤块中分离。由于许多癌细胞的主要扩散途径是局部淋巴结，这些结果指出了一种新的机制，即细胞-细胞黏附缺陷可能导致癌细胞扩散。
Defects in the expression or function of the calcium dependent cell-cell adhesion molecule E-cadherin are common in invasive, metastatic carcinomas. In the present study the response of aggregates of breast epithelial cells and breast and colon carcinoma cells to forces imposed by laminar flow in a parallel plate flow channel was examined. Although E-cadherin negative tumor cells formed cell aggregates in the presence of calcium, these were significantly more likely than E-cadherin positive cell aggregates to disaggregate in response to low shear forces, such as those found in a lymphatic vessel or venule ( 100 dyn/cm2). E-cadherin negative cancer cells which had been transfected with E-cadherin exhibited large increases in adhesion strength only if the expressed protein was appropriately linked to the cytoskeleton. These results show that E-cadherin negative tumor cells, or cells in which the adhesion molecule is present but is inefficiently linked to the cytoskeleton, are far more likely than E-cadherin positive cells to detach from a tumor mass in response to low shear forces, such as those found in a lymphatic vessel or venule. Since a primary route of dissemination of many carcinoma cells is to the local lymph nodes these results point to a novel mechanism whereby defects in cell-cell adhesion could lead to carcinoma cell dissemination.