Martìn-Padura I, Mortarini R, Lauri D, Bernasconi S, Sanchez-Madrid F, Parmiani G, Mantovani A, Anichini A, Dejana E
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Cancer Res. 1991 Apr 15;51(8):2239-41.
Tumor cell attachment to endothelial cells (EC) is one of the critical steps of the metastatic process. It was previously reported that interleukin 1 treatment of EC induces expression of membrane molecules that promote tumor cell adhesion. In this paper we report that a panel of six clones isolated from a human metastatic melanoma presented a marked heterogeneity in their ability to adhere to interleukin 1 activated EC. This was correlated with integrin VLA-4 expression by the clones. Antibodies directed to VLA-4 and to its endothelial ligand INCAM110/VCAM-1 abolished interleukin 1 induced increase in melanoma cell adhesion to EC. These data demonstrate intratumor heterogeneity in the expression of VLA-4 and that this can represent a crucial determinant of tumor cell interaction with EC during secondary spread.
肿瘤细胞与内皮细胞(EC)的附着是转移过程中的关键步骤之一。此前有报道称,用白细胞介素1处理内皮细胞可诱导促进肿瘤细胞黏附的膜分子表达。在本文中,我们报道了从人转移性黑色素瘤中分离出的六个克隆在黏附白细胞介素1激活的内皮细胞的能力上呈现出显著的异质性。这与克隆中整合素VLA - 4的表达相关。针对VLA - 4及其内皮配体INCAM110/VCAM - 1的抗体消除了白细胞介素1诱导的黑色素瘤细胞与内皮细胞黏附增加的现象。这些数据表明肿瘤内VLA - 4表达存在异质性,并且这可能是肿瘤细胞在继发扩散过程中与内皮细胞相互作用的关键决定因素。