Riedel F, Götte K, Schwalb J, Bergler W, Hörmann K
Department of Otolaryngology, Head and Neck Surgery, University Hospital of Mannheim, D-68135 Mannheim, Germany.
Int J Oncol. 2000 Dec;17(6):1099-105. doi: 10.3892/ijo.17.6.1099.
MMP-9, which degrades extracellular matrix, is believed to play a crucial role in tumor invasion and metastasis. Angiogenesis is also perceived as an important step in tumor growth and metastasis. The aim of this study was to investigate the expression of MMP-9 in tumor samples of HNSCC patients and to study a possible correlation to angiogenic markers. Cryostat sections of 52 HNSCC tumors were immunostained for MMP-9, bFGF and VEGF using a standard streptavidin-biotin complex procedure for light microscopic investigation. Microvessel density (MVD) was determined by staining of endothelial cells immunohistochemically using anti-vWF monoclonal antibody. MMP-9 positive staining was detected in 27/52 (52%) of the tumors. MMP-9 immunoreactivity did not correlate with the main clinicopathological characteristics of the patients (localisation, T-stage, N-stage, histological grading), but correlated with worse survival of the patients. MMP-9 negative tumors showed a significant lower mean MVD per microscopic field than MMP-9 positive tumors (p<0. 001). There was a significant association of MMP-9 and VEGF expression (p<0.05). The presence of MMP-9 in HNSCC cancer and the positive correlation with MVD and VEGF expression supports the theory that MMP-9 functions as a regulator of tumor angiogenesis supporting endothelial cell invasion. MMP-9 and VEGF might act co-operatively in the process of neovascularization in human head and neck cancer.
基质金属蛋白酶-9(MMP-9)可降解细胞外基质,被认为在肿瘤侵袭和转移中起关键作用。血管生成也被视为肿瘤生长和转移的重要步骤。本研究的目的是调查头颈部鳞状细胞癌(HNSCC)患者肿瘤样本中MMP-9的表达情况,并研究其与血管生成标志物之间可能存在的相关性。采用标准的链霉亲和素-生物素复合物法对52例HNSCC肿瘤的冰冻切片进行MMP-9、碱性成纤维细胞生长因子(bFGF)和血管内皮生长因子(VEGF)免疫染色,用于光学显微镜观察。通过使用抗血管性血友病因子(vWF)单克隆抗体对内皮细胞进行免疫组织化学染色来测定微血管密度(MVD)。在52例肿瘤中的27例(52%)检测到MMP-9阳性染色。MMP-9免疫反应性与患者的主要临床病理特征(定位、T分期、N分期、组织学分级)无关,但与患者较差的生存率相关。MMP-9阴性肿瘤每高倍视野的平均MVD显著低于MMP-9阳性肿瘤(p<0.001)。MMP-9与VEGF表达之间存在显著关联(p<0.05)。HNSCC癌中MMP-9的存在以及与MVD和VEGF表达的正相关支持了MMP-9作为肿瘤血管生成调节因子支持内皮细胞侵袭的理论。MMP-9和VEGF可能在人类头颈癌的新生血管形成过程中协同作用。