A novel function of CD82/KAI1 in sialyl Lewis antigen-mediated adhesion of cancer cells: Evidence for an anti-metastasis effect by down-regulation of sialyl Lewis antigens

Naoya Yoshihama, Koujiro Yamaguchi, Satomi Chigita, Mariko Mine, Masakazu Abe, Kotaro Ishii, Yosuke Kobayashi, Naonari Akimoto, Yoshihide Mori, Tsuyoshi Sugiura

研究成果: Contribution to journalArticle査読

13 被引用数 (Scopus)

抄録

We have recently elucidated a novel function for CD82 in E-cadherin-mediated homocellular adhesion; due to this function, it can inhibit cancer cell dissociation from the primary cancer nest and limit metastasis. However, the effect of CD82 on selectin ligand-mediated heterocellular adhesion has not yet been elucidated. In this study, we focused on the effects of the metastasis suppressor CD82/KAI1 on heterocellular adhesion of cancer cells to the endothelium of blood vessels in order to further elucidate the function of tetraspanins. The over-expression of CD82 in cancer cells led to the inhibition of experimentally induced lung metastases in mice and significantly inhibited the adhesion of these cells to human umbilical vein epithelial cells (HUVECs) in vitro. Pre-treatment of the cells with function-perturbing antibodies against sLea/x significantly inhibited the adhesion of CD82-negative cells to HUVECs. In addition, cells over-expressing CD82 exhibited reduced expression of sLea/x compared to CD82-negative wild-type cells. Significant down-regulation of ST3 β-galactoside α-2, 3-sialyltransferase 4 (ST3GAL4) was detected by cDNA micro-array, real-time PCR, and western blotting analyses. Knockdown of ST3GAL4 on CD82-negative wild-type cells inhibited expression of sLex and reduced cell adhesion to HUVECs. We concluded that CD82 decreases sLea/x expression via the down-regulation of ST3GAL4 expression and thereby reduces the adhesion of cancer cells to blood vessels, which results in inhibition of metastasis.

本文言語英語
論文番号e0124743
ジャーナルPloS one
10
4
DOI
出版ステータス出版済み - 4 29 2015

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 一般

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