CD147 as a Novel Target in Head and Neck Cancer

描述（由申请方提供）：细胞外基质金属蛋白酶诱导剂（EMMPRIN或CD 147）是一种肿瘤细胞表面分子，已知可促进上皮恶性肿瘤的肿瘤生长，并在头颈部鳞状细胞癌（HNSCC）中高度表达。我们假设CD 147可以作为头颈癌的治疗靶点。我们建议评估抗CD 147抗体单独治疗和联合放疗和顺铂治疗的潜力。此外，我们建议确定CD 147在促进区域转移中的作用。尽管已知CD 147刺激成纤维细胞产生基质金属蛋白酶（MMP）和血管内皮生长因子（VEGF），但我们已经鉴定了在CD 147刺激的成纤维细胞中白细胞介素-12（IL- 12）的上调和分泌。我们建议确定CD 147是否通过调节IL-12在体外和体内肿瘤中促进恶性表型。 公共卫生相关性：头颈癌（HNSCC）的生存率在过去30年中没有显着改善，尽管更积极的治疗和医学治疗的进步。开发针对促进肿瘤生长的分子的靶向药物，当与常规细胞毒性疗法结合时，有可能改善患者的结局。我们建议确定细胞外基质金属蛋白酶诱导剂（EMMPRIN或CD 147）是否是HNSCC的潜在分子靶点。该申请还试图使用头颈癌的鼠原位模型来鉴定CD 147在肿瘤生长和转移中的作用。此外，新的分子机制，CD 147的行为，以促进恶性表型在体外和体内将进行调查。

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.