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.