Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells.
Cell adhesion in a dynamic flow system as compared to static system. Glycosphingolipid-glycosphingolipid interaction in the dynamic system predominates over lectin- or integrin-based mechanisms in adhesion of B16 melanoma cells to non-activated endothelial cells.
复制标题
与静态系统相比，动态流动系统中的细胞粘附。
DOI：
10.1016/s0021-9258(18)41921-7
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Sen
中科院分区：
文献类型：
--
作者：
Naoya Kojima;M. Shiota;Y. Sadahira;K. Handa;Sen
B16黑色素瘤变体与未活化内皮细胞的初始粘附通过黑色素瘤细胞上表达的GM 3（NeuAc α 2- 3Gal β 1- 4Glc β 1-Cer）和内皮细胞上表达的乳糖神经酰胺（LacCer，Gal β 1- 4Glc β 1-Cer）之间的特异性相互作用介导。在采用平行板层流室的动态流动实验系统中，这种粘附优于整联蛋白或凝集素介导的粘附（Lawrence，M. B.，史密斯角，澳-地W.，Eskin，S. G.，McIntire，L.（1990）Blood 75，227-237）。在这个系统中，肿瘤细胞悬浮液流过涂有鞘糖脂、凝集素或纤连蛋白的玻璃板，并在录像带上记录粘附。设计这些条件以模拟发生肿瘤转移沉积的微血管环境。相反，凝集素和纤连蛋白为基础的机制是占主导地位的，在以前使用的静态粘附系统。在静态条件下，四种B16变体与内皮细胞或LacCer包被的板的相对粘附程度与它们的GM 3表达的相对程度相同（即BL 6约F10大于F1大于WA 4），并且在甲基-β-乳糖苷或含有LacCer或GM 3的脂质体存在下粘附受到抑制。用抗GM 3抗体DH 2或唾液酸酶预处理B16细胞和用抗LacCer抗体T5 A7预处理内皮细胞也抑制粘附。在动态流动条件下，WA 4细胞在高剪切应力（大于2.5达因/cm 2）下不粘附于小鼠内皮细胞，但在较低剪切应力下粘附。相反，BL 6和F10细胞在低和高剪切应力下均强烈粘附。在抗体DH 2、乙基-β-乳糖苷或乳糖的存在下，以及通过用唾液酸酶预处理BL 6细胞，在低剪切应力和高剪切应力下BL 6细胞与内皮细胞的粘附被抑制。因此，一些明显的差异，以及相似之处，在静态与动态条件下的细胞粘附证明。这些结果表明，黑色素瘤细胞粘附于内皮细胞，基于GM 3/LacCer相互作用，启动转移沉积，这可能触发一系列“级联”反应，导致内皮细胞活化和IG家族或选择素受体的表达，从而促进肿瘤细胞的粘附和迁移。
Initial adhesion of B16 melanoma variants to non-activated endothelial cells is mediated through specific interaction between GM3 (NeuAc alpha 2—-3Gal beta 1—-4Glc beta 1—-Cer) expressed on melanoma cells and lactosylceramide (LacCer, Gal beta 1—-4Glc beta 1—-Cer) expressed on endothelial cells. This adhesion is predominant over integrin- or lectin-mediated adhesion in a dynamic flow experimental system employing a parallel plate laminar flow chamber (Lawrence, M. B., Smith, C. W., Eskin, S. G., and McIntire, L. V. (1990) Blood 75, 227-237). In this system, a tumor cell suspension flows over a glass plate coated with glycosphingolipid, lectin, or fibronectin, and adhesion is recorded on videotape. These conditions were designed to mimic the microvascular environment in which tumor metastatic deposition takes place. In contrast, lectin- and fibronectin-based mechanisms are predominant in previously used static adhesion systems. Under static conditions, the relative degree of adhesion of the four B16 variants to endothelial cells or to LacCer-coated plates was the same as their relative degree of GM3 expression (i.e. BL6 approximately F10 greater than F1 greater than WA4), and adhesion was inhibited in the presence of methyl-beta-lactoside, or liposomes containing LacCer or GM3. Adhesion was also inhibited by pretreatment of B16 cells with anti-GM3 antibody DH2 or sialidase and by pretreatment of endothelial cells with anti-LacCer antibody T5A7. Under dynamic flow conditions, WA4 cells did not adhere to mouse endothelial cells at high shear stress (greater than 2.5 dynes/cm2) but did adhere at lower shear stress. In contrast, BL6 and F10 cells adhered strongly at both low and high shear stress. BL6 cell adhesion to endothelial cells at both low and high shear stress was inhibited in the presence of antibody DH2, ethyl-beta-lactoside, or lactose, as well as by pretreatment of BL6 cells with sialidase. Thus, some clear differences, as well as similarities, in cell adhesion under static versus dynamic conditions are demonstrated. These findings suggest that melanoma cell adhesion to endothelial cells, based on GM3/LacCer interaction, initiates metastatic deposition, which may trigger a series of “cascade” reactions leading to activation of endothelial cells and expression of Ig family or selectin receptors, thereby promoting adhesion and migration of tumor cells.