Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany
Department of Otorhinolaryngology Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany.
Anticancer Res. 2014 Sep;34(9):4929-37.
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world. While the incidence of HNSCC associated with tobacco and alcohol abuse is falling, the incidence of HNSCC associated with human papilloma virus (HPV) is rising. Proliferation, cell migration and formation of metastases are dependent on interactions between the tumor cells, tumor stromal cells and the extracellular matrix (ECM). Degradation of the ECM is a crucial step in the process of local tumor infiltration and formation of locoregional and distant metastases. Matrix metalloproteinases (MMPs) are a family of enzymes that are able to degrade the ECM. Locally advanced HNSCC with cervical node metastases are treated with docetaxel in induction chemotherapy (ICT) combined with platinum-based chemotherapy and 5-fluorouracil (5-FU) as standard clinical anti-neoplastic regimens. This study evaluated the expression of MMP-14 and MMP-2 in HPV-positive (CERV196) and HPV-negative squamous cell carcinoma (HNSCC 11A and 14C) and the alteration of expression levels after exposure to either docetaxel or 5-FU.
Tumor cells were exposed to 5-FU or docetaxel in concentrations of 1.0 and 5.0 μmol/ml. MMP-protein expression was evaluated by enzyme-linked immunosorbent assay (ELISA) after 2, 3, 5, 8 and 10 days of incubation.
Docetaxel exposure significantly decreased MMP-14 expression in HNSCC 11A and especially 14C but not in CERV196 apart from an apoptotic process. 5-FU had no significant effect on MMP-14 expression independent of the HPV-status. Significant alterations of MMP-2 could be detected in HNSCC 11A only.
Although neither of the applied drugs were selective inhibitors of MMP-expression, surprisingly docetaxel significantly decreased MMP-14 in HNSCC 14C and 11A in this study. Interestingly, HPV-positive CERV196 was not sensitive to decreased MMP-14 or -2 expression following incubation with 5-FU or docetaxel.
头颈部鳞状细胞癌（HNSCC）是世界上第六种最常见的癌症。虽然与烟草和酗酒相关的 HNSCC 发病率正在下降，但与人类乳头瘤病毒（HPV）相关的 HNSCC 发病率正在上升。增殖、细胞迁移和转移的形成依赖于肿瘤细胞、肿瘤基质细胞和细胞外基质（ECM）之间的相互作用。ECM 的降解是局部肿瘤浸润和形成局部和远处转移的关键步骤。基质金属蛋白酶（MMPs）是一类能够降解 ECM 的酶。局部晚期伴颈部淋巴结转移的 HNSCC 采用多西紫杉醇诱导化疗（ICT）联合铂类化疗和氟尿嘧啶（5-FU）作为标准临床抗肿瘤方案进行治疗。本研究评估了 HPV 阳性（CERV196）和 HPV 阴性鳞状细胞癌（HNSCC 11A 和 14C）中 MMP-14 和 MMP-2 的表达，并评估了暴露于多西紫杉醇或 5-FU 后表达水平的变化。
肿瘤细胞以 1.0 和 5.0 μmol/ml 的浓度暴露于 5-FU 或多西紫杉醇。孵育 2、3、5、8 和 10 天后，通过酶联免疫吸附试验（ELISA）评估 MMP-蛋白表达。
除了凋亡过程外，多西紫杉醇暴露显著降低了 HNSCC 11A 中 MMP-14 的表达，尤其是在 14C 中，但在 CERV196 中没有。5-FU 对 HPV 状态无关的 MMP-14 表达没有显著影响。仅在 HNSCC 11A 中可检测到 MMP-2 的显著变化。
尽管应用的两种药物都不是 MMP 表达的选择性抑制剂，但令人惊讶的是，在本研究中，多西紫杉醇显著降低了 HNSCC 14C 和 11A 中的 MMP-14。有趣的是，HPV 阳性的 CERV196 对 5-FU 或多西紫杉醇孵育后 MMP-14 或 -2 表达的降低不敏感。
