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Possible significance of VLA‐4 (α β1) for hematogenous metastasis of renal‐cell cancer
Author(s) -
Tomita Yoshihiko,
Saito Toshihiro,
Saito Kazuhide,
Oite Takashi,
Shimizu Fujio,
Sato Shotaro
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910600604
Subject(s) - renal cell carcinoma , metastasis , cell adhesion molecule , pathology , immunohistochemistry , cancer research , cancer , cell culture , antibody , circulating tumor cell , biology , medicine , immunology , genetics
Very late antigen‐4 (VLA‐4) composed of α and β, a member of the β ‐integrin subfamily, facilitates cell‐to‐cell interaction with vascular celladhesion molecule‐1 (VCAM‐1) on endothelial cells (EC). Attachment of bloodborne 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. Renalcell cancer (RCC) reveals proportionally greater percentages of metastases than other carcinomas at initial diagnosis. We investigated whether VLA‐4 is expressed on RCC, and how such expression on RCC correlates with the metastatic potential of RCC. Immunohistochemical staining on 66 primary and 4 metastatic RCC showed that 4 out of 4 metastatic and 5 out of 8 primary RCC from patients with lung and /or brain metastases expressed α4 and β1 chains. On the other hand, 13 of 58 RCC without metastases expressed α4 chain. α4 and β expressions were also detected on 5 out of 5 human RCC cell lines, ACHN,KRC/Y, A498, Caki1 and Caki2, by flowcytometric analysis. Reversetranscriptasepolymerasechainreaction (RT‐PCR), followed by Southernblot hybridization with cDNA probe for a α4 chain, also confirmed mRNA production in 4 out of 5 RCC cell lines. Furthermore, adhesion of α4‐positive RCC cell lines to human umbilicalvein endothelial cells (HUVEC) was augmented by treatment of HUVEC with tumor necrosis factor‐α (TNF‐α). This adhesion was inhibited by anti‐α4 or anti‐VCAM‐1 antibodies, suggesting that VLA‐4‐VCAM‐1 interaction was involved in the adhesion between RCC cells and HUVEC. Taken together, VLA‐4 on RCC cells might play a crucial role in their hematogenous metastasis. © 1995 Wiley‐Liss. Inc.