Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density.
Carbonic anhydrase IX, an endogenous hypoxia marker, expression in head and neck squamous cell carcinoma and its relationship to hypoxia, necrosis, and microvessel density.
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DOI：
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发表时间：
2001-07
期刊：
影响因子：
11.2
通讯作者：
N. Beasley;C. Wykoff;P. Watson;R. Leek;H. Turley;K. Gatter;J. Pastorek;G. Cox;P. Ratcliffe;A. Harris
中科院分区：
文献类型：
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作者：
N. Beasley;C. Wykoff;P. Watson;R. Leek;H. Turley;K. Gatter;J. Pastorek;G. Cox;P. Ratcliffe;A. Harris
碳酸酐酶IX （CA IX）是一种具有活性胞外酶位点的跨膜糖蛋白。我们以前已经证明它是缺氧诱导的，因此可能是缺氧的内源性标记。它在某些肿瘤中过度表达，尤其是肾细胞癌。本研究的目的是检测头颈部鳞状细胞癌（HNSCC）中CA IX的表达和定位，并将其与肿瘤微血管的位置、血管生成、坏死和分期联系起来。采用免疫印迹法检测常氧和低氧（pO(2) 0.1%）培养的3株HNSCC细胞株和3对HNSCC肿瘤和正常组织样本中CA IX的表达。保存的HNSCC石蜡切片（79）用CA IX和CD34抗体免疫染色，测定微血管密度（MVD）。通过CA IX和CD34双染色切片，计算血管与CA IX表达和坏死开始的距离。caix在缺氧诱导下在所有三种HNSCC细胞系中均存在，并在HNSCC肿瘤组织中过表达。在免疫染色上，肿瘤的过表达局限于肿瘤的坏疽区，在单因素分析上，表达CA IX的肿瘤面积百分比显著高于肿瘤坏死（P = 0.001）、高MVD （P = 0.02）和晚期（P = 0.033），在多因素分析上，肿瘤坏死（P = 0.0003）和MVD （P = 0.0019）。血管与caix表达起始点的中位距离为80微米（范围40-140微米）。由于缺氧，caix在HNSCC中过表达，是该肿瘤中缺氧的潜在生物标志物。过表达可能有助于维持细胞内pH值，使肿瘤细胞具有生存优势，增强对放疗和化疗的抵抗力。CA IX是HNSCC未来治疗的潜在靶点。
Carbonic anhydrase IX (CA IX) is a transmembrane glycoprotein with an active extracellular enzyme site. We have shown previously that it was hypoxia inducible and may therefore be an endogenous marker of hypoxia. It is overexpressed in some tumors, particularly renal cell carcinoma. The aim of this study was to examine the expression and localization of CA IX in head and neck squamous cell carcinoma (HNSCC) and relate this to the location of tumor microvessels, angiogenesis, necrosis, and stage. Expression of CA IX was determined by immunoblotting in three HNSCC cell lines grown in normoxia and hypoxia (pO(2) 0.1%) and three paired tumor and normal tissue samples of HNSCC. Archived paraffin sections (79) of HNSCC were immunostained with antibodies to CA IX and CD34 to determine microvessel density (MVD). By double staining sections with CA IX and CD34, the distance between blood vessels and the start of CA IX expression and necrosis was calculated. CA IX was induced by hypoxia in all three HNSCC cell lines and overexpressed in HNSCC tumor tissue. Overexpression was localized to the perinecrotic area of the tumor on immunostaining, and the percentage area of the tumor expressing CA IX was significantly higher with more tumor necrosis (P = 0.001), a high MVD (P = 0.02), and advanced stage (P = 0.033) on univariate analysis and necrosis (P = 0.0003) and MVD (P = 0.0019) on multivariate analysis. The median distance between a blood vessel and the start of CA IX expression was 80 microm (range, 40-140 microm). CA IX is overexpressed in HNSCC because of hypoxia and is a potential biomarker for hypoxia in this tumor. Overexpression may help to maintain the intracellular pH, giving tumor cells a survival advantage and enhancing resistance to radiotherapy and chemotherapy. CA IX is a potential target for future therapy in HNSCC.