Department of Surgery, University of Alabama at Birmingham, USA.
Anticancer Drugs. 2010 Oct;21(9):861-7. doi: 10.1097/CAD.0b013e32833d1a11.
Targeting the molecular pathways associated with carcinogenesis remains the greatest opportunity to reduce treatment-related morbidity and mortality. Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a cell surface molecule known to promote tumor growth and angiogenesis in preclinical studies of head and neck carcinoma making it an excellent therapeutic target. To evaluate the feasibility of anti-EMMPRIN therapy, an ex-vivo human head and neck cancer model was established using specimens obtained at the time of surgery (n=22). Tumor slices were exposed to varying concentrations of anti-EMMPRIN monoclonal antibody and cetuximab for comparison purposes. Cetuximab is the only monoclonal antibody currently approved for the treatment of head and neck carcinoma. After treatment, tumor slices were assessed by immunohistochemistry and western blot analysis for apoptosis (TUNEL) and EMMPRIN expression. Of the tumor specimens 33% showed a significant reduction in mean ATP levels after treatment with cetuximab compared with untreated controls, whereas 58% of the patients responded to anti-EMMPRIN therapy (P<0.05). Samples, which showed reactivity to anti-EMMPRIN, also had greater EMMPRIN expression based on immunohistochemistry staining (49%) when compared with nonresponders (25%, P=0.06). In addition, TUNEL analysis showed a larger number of cells undergoing apoptosis in antibody-treated tumor slices (77%) compared with controls (30%, P<0.001) with activation of apoptotic proteins, caspase 3 and caspase 8. This study shows the potential of anti-EMMPRIN to inhibit proliferation and promote apoptosis and suggests its future role in the targeted treatment of head and neck carcinoma.
针对与癌变相关的分子途径仍然是降低治疗相关发病率和死亡率的最大机会。细胞外基质金属蛋白酶诱导剂（EMMPRIN），也称为 CD147，是一种已知在头颈部癌的临床前研究中促进肿瘤生长和血管生成的细胞表面分子，使其成为一个极好的治疗靶点。为了评估抗-EMMPRIN 治疗的可行性，使用手术时获得的标本建立了体外人头颈部癌症模型（n=22）。为了比较，将肿瘤切片暴露于不同浓度的抗-EMMPRIN 单克隆抗体和西妥昔单抗。西妥昔单抗是目前唯一批准用于治疗头颈部癌的单克隆抗体。治疗后，通过免疫组织化学和 Western blot 分析评估肿瘤切片的细胞凋亡（TUNEL）和 EMMPRIN 表达。与未经处理的对照组相比，在用西妥昔单抗治疗后，有 33%的肿瘤标本的平均 ATP 水平显著降低，而 58%的患者对抗-EMMPRIN 治疗有反应（P<0.05）。与无反应者（25%，P=0.06）相比，对 EMMPRIN 有反应的样本基于免疫组织化学染色也具有更高的 EMMPRIN 表达（49%）。此外，TUNEL 分析显示，在抗体处理的肿瘤切片中，细胞凋亡的数量更多（77%），而在对照组中为 30%（P<0.001），同时激活了凋亡蛋白，如 caspase 3 和 caspase 8。这项研究表明抗-EMMPRIN 抑制增殖和促进凋亡的潜力，并暗示其在头颈部癌靶向治疗中的未来作用。
