[Possible significance of VLA-4 (alpha 4 beta 1) for hematogenous metastasis of renal cell cancer]

Abstract

Very late antigen-4 (VLA-4) composed of alpha 4 and beta 1, a member of the beta 1-integrin subfamily, facilitates cell-to-cell interaction with vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells (EC). Attachment of blood-borne tumor cells to EC is a crucial step for hematogenous metastasis, and VLA-4-positive tumor cells can attach to EC by binding to VCAM-1. Renal cell cancer (RCC) reveals proportionally greater percentage of metastasis among other carcinomas at an initial diagnosis. We investigated whether VLA-4 is expressed on RCC and how such expression on RCC correlates with metastatic potential of RCC. Immunohistochemical staining on 66 primary and 4 metastatic RCCs showed that 4 of 4 metastatic and 5 of 8 primary RCCs (72.5%) from patients with lung and/or brain metastasis expressed alpha 4 and beta 1 chains. On the other hand, 13 of 58 (22.4%) RCCs without metastasis expressed alpha 4 chain. alpha 4 and beta 1 expressions were also detected on 5 of 5 human RCC cell lines by flowcytometer analysis. RT-PCR followed by Southern blot hybridization also confirmed mRNA production in 4 of 5 RCC cell lines. Furthermore, adhesion of alpha 4-positive RCC cell lines to human umbilical vein endothelial cells (HUVECs) was augmented by a treatment of HUVECs with Tumor necrosis factor-alpha (TNF-alpha) or IL-4 thorough increase of VCAM-1 expression. These adhesion were inhibited by anti-alpha 4 or anti-VCAM-1 antibodies suggesting that VLA-4-VCAM-1 interaction was involved in the adhesion between RCC cells and HUVECs.(ABSTRACT TRUNCATED AT 250 WORDS)