Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma
Cyclophilin A-EMMPRIN interaction induces invasion of head and neck squamous cell carcinoma
复制标题
DOI：
10.3892/or.2011.1474
复制
发表时间：
2012-01-01
期刊：
影响因子：
4.2
通讯作者：
Ishikawa, Kazuo
中科院分区：
文献类型：
--
作者：
Takahashi, Masafumi;Suzuki, Shinsuke;Ishikawa, Kazuo
细胞外基质重塑对肿瘤的发生至关重要，涉及蛋白水解酶，主要是基质金属蛋白酶(MMPs)。基质金属蛋白酶的产生受到多种因素的刺激，包括细胞外基质金属蛋白酶诱导因子EMMPRIN/CD147。作为免疫球蛋白超家族的一员，EMMPRIN的过表达可促进肿瘤细胞的侵袭、转移、生长和存活。亲环素A(CypA)是一种多功能蛋白质，可促进各种癌症类型的癌症进展。CypA可以与EMMPRIN相互作用并激活EMMPRIN；然而，CypA-EMMPRIN相互作用在致癌中的作用尚不完全清楚。为了研究CypA-EMMPRIN相互作用诱导的致瘤性，我们用CypA刺激表达EMMPRIN的头颈部鳞状细胞癌(HNSCC)细胞。3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium比色法显示，细胞在CypA刺激下增殖增加，而顺铂诱导的细胞死亡减少。明胶酶谱显示CypA还可诱导MMP9表达上调。此外，在CypA刺激下，HNSCC细胞通过Matrigel(TM)涂层膜的侵袭力增加。这种升高的侵袭潜能被EMMPRIN功能阻断抗体消除。这些发现表明，CypA通过与EMMPRIN的相互作用促进了HNSCC的肿瘤发生。
Extracellular matrix remodeling crucial to tumorigenesis involves proteolytic enzymes, primarily matrix metalloproteinases (MMPs). MMP production is stimulated by multiple factors, including the extracellular matrix metalloproteinase 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 (TM)-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.