Connexin 45 is a novel suppressor of melanoma metastasis.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2023-04-01 Epub Date: 2022-12-17 DOI:10.1007/s10616-022-00563-x

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

{"title":"Connexin 45 is a novel suppressor of melanoma metastasis.","authors":"Mikako Saito, Naruwa Tokunaga, Toshiki Saito, Tomohiro Hatakenaka, Tomonori Sasaki, Nahoko Matsuki, Seiya Minagawa","doi":"10.1007/s10616-022-00563-x","DOIUrl":null,"url":null,"abstract":"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 Cx45 was found among 20 isoforms. The expression level of Cx45 was highest in F1 and lowest in BL6. It was inductively predicted that Cx45 might be a novel suppressor of metastasis. A Cx45-overexpressing BL6 cell line (Cx45 +BL6) was developed and its properties were compared with those of a wild-type cell line of BL6 (W-BL6). Compared to W-BL6, Cx45 +BL6 showed reduced wound healing, Transwell® permeability, and matrix metalloproteinase 9 expression, suggesting the suppression of cellular migration and invasion. The expression of E-cadherin and integrin β1 in Cx45 +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 Cx45 +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 Cx45 +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.","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10030756/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s10616-022-00563-x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/12/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}

引用次数: 0

Abstract

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 Cx45 was found among 20 isoforms. The expression level of Cx45 was highest in F1 and lowest in BL6. It was inductively predicted that Cx45 might be a novel suppressor of metastasis. A Cx45-overexpressing BL6 cell line (Cx45 ⁺BL6) was developed and its properties were compared with those of a wild-type cell line of BL6 (W-BL6). Compared to W-BL6, Cx45 ⁺BL6 showed reduced wound healing, Transwell® permeability, and matrix metalloproteinase 9 expression, suggesting the suppression of cellular migration and invasion. The expression of E-cadherin and integrin β1 in Cx45 ⁺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 Cx45 ⁺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 Cx45 ⁺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.

Abstract Image

查看原文本刊更多论文

Connexin 45 是一种新型的黑色素瘤转移抑制因子。

研究了三种小鼠黑色素瘤细胞系中连接蛋白（Cx）同工酶的表达谱：B16-F1（F1）、B16-F10（F10）和B16-BL6（BL6）。转移潜能强度依次为 F1、F10 和 BL6。在 20 种同工酶中，Cx45 的表现引人注目。Cx45的表达水平在F1中最高，在BL6中最低。据此推断，Cx45可能是一种新型的转移抑制因子。研究人员建立了一个表达Cx45的BL6细胞系（Cx45 +BL6），并将其特性与野生型BL6细胞系（W-BL6）进行了比较。与W-BL6相比，Cx45 +BL6的伤口愈合、Transwell®渗透性和基质金属蛋白酶9的表达均有所降低，这表明细胞的迁移和侵袭受到了抑制。Cx45 +BL6中E-cadherin和整合素β1的表达也低于W-BL6，表明细胞粘附性降低。细胞冲洗试验证实了细胞粘附性的降低。相比之下，W-BL6 和 Cx45 +BL6 在细胞增殖方面没有差异，这表明它们对细胞周期调节因子没有影响。最后，体内试验显示，在小鼠模型中，Cx45 +BL6 的转移菌落数（176 ± 25/肺）与 W-BL6 的转移菌落数（252 ± 23/肺）相比显著减少。总之，Cx45是一种新型的黑色素瘤转移抑制因子：在线版本包含补充材料，可查阅 10.1007/s10616-022-00563-x。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464