Connexin 45 is a novel suppressor of melanoma metastasis.

IF 2 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Cytotechnology 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

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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.

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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。

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来源期刊

Cytotechnology 生物-生物工程与应用微生物

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The scope of the Journal includes: 1. The derivation, genetic modification and characterization of cell lines, genetic and phenotypic regulation, control of cellular metabolism, cell physiology and biochemistry related to cell function, performance and expression of cell products. 2. Cell culture techniques, substrates, environmental requirements and optimization, cloning, hybridization and molecular biology, including genomic and proteomic tools. 3. Cell culture systems, processes, reactors, scale-up, and industrial production. Descriptions of the design or construction of equipment, media or quality control procedures, that are ancillary to cellular research. 4. The application of animal/human cells in research in the field of stem cell research including maintenance of stemness, differentiation, genetics, and senescence, cancer research, research in immunology, as well as applications in tissue engineering and gene therapy. 5. The use of cell cultures as a substrate for bioassays, biomedical applications and in particular as a replacement for animal models.