CD147 as a Novel Target in Head and Neck Cancer

描述(申请人提供)：细胞外基质金属蛋白酶诱导物(EMMPRIN或CD147)是一种肿瘤细胞表面分子，已知在上皮性恶性肿瘤中促进肿瘤生长，在头颈部鳞状细胞癌(HNSCC)中高表达。我们假设CD147可以作为头颈癌的治疗靶点。我们建议评估抗CD147抗体单独治疗以及联合放射治疗和顺铂治疗的可能性。此外，我们建议确定CD147在促进区域转移中的作用。虽然已知CD147可刺激成纤维细胞产生基质金属蛋白酶(MMPs)和血管内皮生长因子(VEGF)，但我们已发现CD147刺激成纤维细胞上调和分泌IL-12。我们建议确定CD147是否通过调节IL-12在体内和体外促进肿瘤的恶性表型。 公共卫生相关性：尽管治疗更加积极，医疗治疗也取得了进步，但头颈部癌症(HNSCC)的存活率在过去30年中并没有显著改善。开发针对促进肿瘤生长的分子的靶向药物，当与传统的细胞毒治疗相结合时，有可能改善患者的预后。我们建议确定细胞外基质金属蛋白酶诱导物(EMMPRIN或CD147)是否为HNSCC的潜在分子靶点。该应用程序还试图通过小鼠头颈部癌原位模型来确定CD147在肿瘤生长和转移中的作用。此外，CD147在体外和体内促进恶性表型的新的分子机制将被研究。

DESCRIPTION (provided by applicant): Extracellular matrix metalloprotease inducer (EMMPRIN or CD147) is a tumor cell surface molecule that is known to promote tumor growth in epithelial malignancies and is highly expressed in head and neck squamous cell carcinoma (HNSCC). We hypothesize that CD147 can be exploited as a therapeutic target in head and neck cancer. We propose to assess the potential of anti-CD147 antibody therapy alone and in combination with concurrent radiation and cisplatin treatment. Furthermore, we propose to determine the role of CD147 in promoting regional metastasis. Although CD147 is known to stimulate fibroblasts to produce matrix metalloproteases (MMPs) and vascular endothelial growth factor (VEGF), we have identified upregulation and secretion of interleukin-12 (IL- 12) in CD147 stimulated fibroblasts. We propose to determine if CD147 promotes the malignant phenotype in vitro and in vivo tumor through modulation of IL-12. PUBLIC HEALTH RELEVANCE: Survival rates for head and neck cancer (HNSCC) have not significantly improved over the past 30 years despite more aggressive treatment and advances in medical treatment. Development of targeted agents against molecules that promote tumor growth have the potential to improve patient outcomes when combined with conventional cytotoxic therapies. We propose to determine if extracellular matrix metalloprotease inducer (EMMPRIN or CD147) is a potential molecular target in HNSCC. The application also seeks to identify the role of CD147 in tumor growth and metastasis using murine orthotopic models of head and neck cancer. Furthermore, novel molecular mechanisms by which CD147 acts to promote the malignant phenotype in vitro and in vivo will be investigated.