连接蛋白45是黑色素瘤转移的一种新型抑制因子。

Connexin 45 is a novel suppressor of melanoma metastasis.

作者信息

Saito Mikako, Tokunaga Naruwa, Saito Toshiki, Hatakenaka Tomohiro, Sasaki Tomonori, Matsuki Nahoko, Minagawa Seiya

机构信息

Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16, Naka-cho, Koganei, 184-8588 Tokyo, Japan.

出版信息

Cytotechnology. 2023 Apr;75(2):103-113. doi: 10.1007/s10616-022-00563-x. Epub 2022 Dec 17.

DOI:10.1007/s10616-022-00563-x

PMID:36969569

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10030756/

Abstract

UNLABELLED

The expression spectra of connexin (Cx) isoforms were investigated in three mouse melanoma cell lines: B16-F1 (F1), B16-F10 (F10), and B16-BL6 (BL6). Metastatic potential intensity was higher in the order of F1, F10, and BL6. A remarkable behavior of was found among 20 isoforms. The expression level of was highest in F1 and lowest in BL6. It was inductively predicted that might be a novel suppressor of metastasis. A -overexpressing BL6 cell line ( BL6) was developed and its properties were compared with those of a wild-type cell line of BL6 (W-BL6). Compared to W-BL6, BL6 showed reduced wound healing, Transwell® permeability, and matrix metalloproteinase 9 expression, suggesting the suppression of cellular migration and invasion. The expression of and in BL6 was also lower than in W-BL6, suggesting reduced cell adhesion. The decrease in cell adhesion was supported by the cell washing-out assay. In contrast, no difference between W-BL6 and BL6 was observed in cell proliferation, suggesting no effect on cell-cycle regulating factors. Finally, an in vivo assay revealed a significant decrease in the number of metastatic colonies of BL6 (176 ± 25/lung) in comparison with those of W-BL6 (252 ± 23/lung) in a mouse model. In conclusion, Cx45 is a novel suppressor of melanoma metastasis.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1007/s10616-022-00563-x.

摘要

未标记

在三种小鼠黑色素瘤细胞系中研究了连接蛋白（Cx）亚型的表达谱：B16-F1（F1）、B16-F10（F10）和B16-BL6（BL6）。转移潜能强度按F1、F10和BL6的顺序升高。在20种亚型中发现了一种显著的行为。其表达水平在F1中最高，在BL6中最低。据推测，它可能是一种新型的转移抑制因子。构建了过表达该因子的BL6细胞系（该BL6），并将其特性与野生型BL6细胞系（W-BL6）进行比较。与W-BL6相比，该BL6的伤口愈合、Transwell®通透性和基质金属蛋白酶9表达降低，表明细胞迁移和侵袭受到抑制。该BL6中该因子和另一因子的表达也低于W-BL6，表明细胞黏附减少。细胞洗脱试验支持了细胞黏附的降低。相比之下，W-BL6和该BL6在细胞增殖方面未观察到差异，表明对细胞周期调节因子无影响。最后，体内试验显示，在小鼠模型中，该BL6的转移集落数量（176±25/肺）与W-BL6（252±23/肺）相比显著减少。总之，Cx45是黑色素瘤转移的新型抑制因子。