Soni Shilpi, Mathur Meera, Shukla Nootan K, Deo Suryanarayan V S, Ralhan Ranju
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Int J Cancer. 2003 Nov 1;107(2):309-16. doi: 10.1002/ijc.11366.
Stromelysin-3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco-associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT-PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial-to-mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety-eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan-Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis.
基质溶解素-3（ST3/MMP11）与人类肿瘤进展相关。为确定ST3在口腔肿瘤发生中的临床意义，分析了其在烟草相关口腔癌不同阶段的表达情况。对79例口腔癌前病变、177例鳞状细胞癌和35例组织学正常的口腔组织进行了ST3表达的免疫组织化学分析，并通过免疫印迹和逆转录-聚合酶链反应进行了验证。在45/79（57%）的癌前病变中观察到ST3/MMP11蛋白表达[28/48（58%）为增生性病变，17/31（55%）为发育异常性病变]，在123/177（70%）的口腔鳞状细胞癌中也观察到该蛋白表达。在癌前病变中，ST3表达高于正常口腔组织（p = 0.000），且与微血管密度（MVD，血管生成标志物）相关（p = 0.05）。ST3也在经历上皮-间质转化的癌前和癌性病变培养的细胞中表达。在口腔癌患者中，ST3阳性与淋巴结受累相关（p = 0.025），且肿瘤内MVD增加（p = 0.009）。对98例口腔鳞状细胞癌患者进行了为期94个月（中位时间22.5个月）的随访。Kaplan-Meier生存分析表明，ST3表达不是一个显著的预后指标。ST3在口腔增生性和发育异常性病变中的表达表明其与口腔上皮恶性转化途径早期获得的表型改变进展相关，提示其不仅参与血管生成和侵袭，还参与肿瘤发生。因此，ST3可能成为开发用于口腔肿瘤发生早期干预的分子治疗药物的潜在靶点。
