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Chloride intracellular channel protein 2 is secreted and inhibits MMP14 activity, while preventing tumor cell invasion and metastasis

Ozaki, Saya ; Umakoshi, Akihiro ; Yano, Hajime ; Ohsumi, Shota ; Sumida, Yutaro ; Hayase, Erika ; Usa, Eika ; Islam, Afsana ; Choudhury, Mohammed E. ; Nishi, Yusuke ; Yamashita, Daisuke ; Ohtsuka, Yoshihiro ; Nishikawa, Masahiro ; Inoue, Akihiro ; Suehiro, Satoshi ; Kuwabara, Jun ; Watanabe, Hideaki ; Takada, Yasutsugu ; Watanabe, Yuji ; Nakano, Ichiro ; Kunieda, Takeharu ; Tanaka, Junya

Neoplasia (New York, N.Y.), 2021-08, Vol.23 (8), p.754-765 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Chloride intracellular channel protein 2 is secreted and inhibits MMP14 activity, while preventing tumor cell invasion and metastasis
Autor: Ozaki, Saya ; Umakoshi, Akihiro ; Yano, Hajime ; Ohsumi, Shota ; Sumida, Yutaro ; Hayase, Erika ; Usa, Eika ; Islam, Afsana ; Choudhury, Mohammed E. ; Nishi, Yusuke ; Yamashita, Daisuke ; Ohtsuka, Yoshihiro ; Nishikawa, Masahiro ; Inoue, Akihiro ; Suehiro, Satoshi ; Kuwabara, Jun ; Watanabe, Hideaki ; Takada, Yasutsugu ; Watanabe, Yuji ; Nakano, Ichiro ; Kunieda, Takeharu ; Tanaka, Junya
Assuntos: Animals ; Benign ; Brain Neoplasms - diagnostic imaging ; Brain Neoplasms - etiology ; Brain Neoplasms - metabolism ; Brain Neoplasms - pathology ; Brain tumor ; Capillary Permeability - genetics ; Cell Line, Tumor ; Cell Movement ; Chloride Channels - genetics ; Chloride Channels - metabolism ; Distant metastasis ; Enzyme Activation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Silencing ; Humans ; Immunohistochemistry ; Invasion ; Malignant ; Matrix Metalloproteinase 14 - genetics ; Matrix Metalloproteinase 14 - metabolism ; Neoplasm Grading ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Neoplasm Staging ; Original Research ; Prognosis ; Protein Binding ; Rats ; Tumor Microenvironment
É parte de: Neoplasia (New York, N.Y.), 2021-08, Vol.23 (8), p.754-765
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Saya Ozaki and Akihiro Umakoshi are the co-first authors.
Descrição: •CLIC2 is highly expressed in benign, less invasive and less metastatic tumors.•Forced expression of CLIC2 prevents metastasis and invasion in animal tumor models.•CLIC2 is associated with decreased vascular permeability in tumor masses.•CLIC2, a secretable soluble protein, can bind to and inhibit MMP14.•Extracellular CLIC2 can suppress malignant cell invasion. The abilities to invade surrounding tissues and metastasize to distant organs are the most outstanding features that distinguish malignant from benign tumors. However, the mechanisms preventing the invasion and metastasis of benign tumor cells remain unclear. By using our own rat distant metastasis model, gene expression of cells in primary tumors was compared with that in metastasized tumors. Among many distinct gene expressions, we have focused on chloride intracellular channel protein 2 (CLIC2), an ion channel protein of as-yet unknown function, which was predominantly expressed in the primary tumors. We created CLIC2 overexpressing rat glioma cell line and utilized benign human meningioma cells with naturally high CLIC2 expression. CLIC2 was expressed at higher levels in benign human brain tumors than in their malignant counterparts. Moreover, its high expression was associated with prolonged survival in the rat metastasis and brain tumor models as well as with progression-free survival in patients with brain tumors. CLIC2 was also correlated with the decreased blood vessel permeability likely by increased contents of cell adhesion molecules. We found that CLIC2 was secreted extracellularly, and bound to matrix metalloproteinase (MMP) 14. Furthermore, CLIC2 prevented the localization of MMP14 in the plasma membrane, and inhibited its enzymatic activity. Indeed, overexpressing CLIC2 and recombinant CLIC2 protein effectively suppressed malignant cell invasion, whereas CLIC2 knockdown reversed these effects. Thus, CLIC2 suppress invasion and metastasis of benign tumors at least partly by inhibiting MMP14 activity. [Display omitted]
Editor: United States: Elsevier Inc
Idioma: Inglês

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Chloride intracellular channel protein 2 is secreted and inhibits MMP14 activity, while preventing tumor cell invasion and metastasis

United States: Elsevier Inc

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