Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma.

Abstract:

:Extracellular matrix remodeling crucial to tumorigenesis involves proteolytic enzymes, primarily matrix metalloproteinases (MMPs). MMP production is stimulated by multiple factors, including the extracellular matrix metallo-proteinase inducer EMMPRIN/CD147. Overexpression of EMMPRIN, a member of the immunoglobulin superfamily, promotes invasion, metastasis, growth and survival of malignant cells. Cyclophilin A (CypA) is a multifunctional protein that promotes cancer progression in various cancer types. CypA can interact with and activate EMMPRIN; however, the role of CypA-EMMPRIN interaction in oncogenicity is not completely understood. To investigate tumorigenicity induced by the CypA-EMMPRIN interaction, we stimulated EMMPRIN-expressing head and neck squamous cell carcinoma (HNSCC) cells with CypA. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye assay revealed that HNSCC cell proliferation increased upon stimulation of the cells with CypA, whereas cisplatin-induced cell death decreased after stimulation. Gelatin zymography showed that CypA also induced MMP-9 up-regulation. Moreover, HNSCC cell invasion through Matrigel™-coated membranes was increased upon stimulation of cells with CypA. This elevated invasive potential was abrogated by an EMMPRIN function-blocking antibody. These findings suggest that CypA, through its interaction with EMMPRIN, contributes to HNSCC tumorigenesis.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Takahashi M,Suzuki S,Ishikawa K

doi

10.3892/or.2011.1474

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

198-203

issue

1

eissn

1021-335X

issn

1791-2431

journal_volume

27

pub_type

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