Singh Jasmine, Naran Anupam, Misso Neil L, Rigby Paul J, Thompson Philip J, Bhoola Kanti D
Lung Institute of Western Australia, Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Perth, Australia.
Int Immunopharmacol. 2008 Feb;8(2):300-6. doi: 10.1016/j.intimp.2007.08.015. Epub 2007 Sep 6.
Lung cancer is currently the leading cause of cancer mortality worldwide. Expression of kallikrein-related peptidases (KRP/hK/KLK) may be induced during lung carcinogenesis. To test the hypothesis that KRP/hK, previously identified in the skin (KRP/hK5, 7) and brain (KRP/hK6, 8), are expressed in lung tumours, experiments were designed to investigate their localization in four malignant sub-types of human lung cancer. Using specific antibodies, expression of these KRP/hK was determined in archived lung tumour sections of the four subtypes, and in normal skin, brain, lung and submandibular gland tissue sections. Immunoperoxidase labelled sections were visualized by brightfield microscopy. In the squamous cell carcinoma, small cell carcinoma and carcinoid tumour, 40-90% of the malignant cells showed positive cytoplasmic labelling for KRP/hK5, 7, 6 and 8 (intensity grade 2+/3+). In the adenocarcinoma there was no cytoplasmic labelling for any of the KRP/hK, but the nuclei of 20% of the tumour cells were labelled for KRP/hK5, 7 and 8 (intensity grade 2+/3+). Further studies are required to determine the functional significance of the expression of KRP/hK in human lung carcinomas, and whether any of these proteins may be potential biomarkers for specific sub-types of lung cancer.
肺癌是目前全球癌症死亡的主要原因。激肽释放酶相关肽酶(KRP/hK/KLK)的表达可能在肺癌发生过程中被诱导。为了验证先前在皮肤(KRP/hK5、7)和大脑(KRP/hK6、8)中发现的KRP/hK在肺肿瘤中表达的假说,设计了实验来研究它们在人类肺癌四种恶性亚型中的定位。使用特异性抗体,在四种亚型的存档肺肿瘤切片以及正常皮肤、大脑、肺和下颌下腺组织切片中测定这些KRP/hK的表达。免疫过氧化物酶标记的切片通过明场显微镜观察。在鳞状细胞癌、小细胞癌和类癌肿瘤中,40%-90%的恶性细胞对KRP/hK5、7、6和8显示阳性细胞质标记(强度等级为2+/3+)。在腺癌中,任何KRP/hK均无细胞质标记,但20%的肿瘤细胞核被标记为KRP/hK5、7和8(强度等级为2+/3+)。需要进一步研究来确定KRP/hK在人类肺癌中表达的功能意义,以及这些蛋白质是否可能是特定亚型肺癌的潜在生物标志物。