Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma
Activation of MMP-2 and MMP-9 in patients with oral squamous cell carcinoma
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DOI：
10.1002/jso.20240
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发表时间：
2005-05-01
影响因子：
2.5
通讯作者：
Patel, PS
中科院分区：
文献类型：
--
作者：
Patel, BP;Shah, PM;Patel, PS
背景和目的：口腔癌占印度所有恶性肿瘤的三分之一，其中烟草消费习惯是导致口腔黏膜现场癌变的主要病因。口腔癌原野癌变引起的口腔黏膜多分子事件可能是口腔癌累及局部和区域淋巴结的原因，导致总生存率低、复发率高、预后差。几种基质金属蛋白酶（MMPs）在口腔鳞状细胞癌（SCC）的侵袭和转移中起重要作用。MMP-2和MMP-9能够降解iv型胶原，而iv型胶原是基底膜的主要成分。因此，我们通过明胶酶谱法研究了口服SCCs患者中MMP-2和MMP-9的激活，以预测其在转移潜力中的作用。明胶酶谱法是ELISA法的一种经济有效的替代方法。材料与方法：39例口腔SCCs患者根据是否累及局部淋巴结分为非转移性（n = 28）和转移性（n = 11）。术中收集患者的恶性及邻近正常组织。在非变性、非还原条件下，采用7.5%聚丙烯酰胺凝胶进行明胶酶谱分析。酶谱进行密度分析。MMP-2和MMP-9的潜伏和活性形式以ng/50杯蛋白表达。结果：恶性肿瘤组织中MMP-2和MMP-9的潜伏和活性水平明显高于癌旁正常组织（P < 0.05）。恶性组织中MMP-2和MMP-9的总活性也明显高于邻近正常组织（P = 0.005和P = 0.028）。恶性组织中MMP-2和MMP-9的活化率明显高于邻近正常组织。在恶性组织中，MMP-2的激活率（11%）高于MMP-9（5%）。淋巴结转移患者的MMP-2活化率明显高于无淋巴结转移患者（P=0.005）。受试者工作特征（ROC）曲线分析显示，MMP-2的激活比在有无淋巴不转移的患者中有更好的区别，MMP-9的激活比在有无淋巴不转移的患者中有更好的区别。MMP-2的激活比可以预测无淋巴结累及患者的淋巴结转移发生风险。结论：恶性组织中MMP-2和MMP-9的活化水平明显高于邻近正常组织。此外，与未发生淋巴结转移的患者相比，淋巴结转移患者的MMP-2激活率显著升高，这可以预测淋巴结阴性患者发生淋巴结转移的风险。(C) 2005 Wiley-Liss, Inc。
Background and Objectives: Oral cancer accounts for one third of all malignancies in India where habit of tobacco consumption is the major etiologic factor, which causes field cancerization in oral mucosa. Multiple molecular events in oral mucosa due to field cancerization may be the cause of local and regional lymph node involvement in oral cancer resulting into low overall survival, high recurrence rate, and poor prognosis. Several matrix metalloproteinases (MMPs) have been shown to play an important role in the invasion and metastasis of oral squamous cell carcinoma (SCC). MMP-2 and MMP-9 are capable of degrading type-IV collagen, which is a major component of basement membrane. Therefore, we studied MMP-2 and MMP-9 activation by gelatin zymography, which is cost effective alternate to ELISA method, in patients with oral SCCs to predict their role in metastatic potentials.Materials and Methods: Thirty-nine patients of oral SCCs were classified as non-metastatic (n = 28), and metastatic (n = 11) according to regional lymph node involvement. Malignant and adjacent normal tissues of the patients Were collected at the time of surgery. Gelatin zymography was carried out using 7.5% polyacrylamide gel under non-denaturing and non-reducing conditions. Zymograms were analyzed densitometrically. Latent and active forms of MMP-2 and MMP-9 were expressed as ng/50 mug of protein.Results: Latent and active forms of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared to their adjacent normal tissues (P < 0.05). Total MMP-2 and MMP-9 activities were also significantly elevated in malignant tissues as compared to adjacent normal tissues (P = 0.005 and P = 0.028, respectively). Activation ratio of MMP-2 and MMP-9 were significantly elevated in malignant tissues as compared to adjacent normal tissues. Activation of MMP-2 was prominent (11%) than MMP-9 (5%) in malignant tissues. Activation ratio of MMP-2 was significantly elevated in patients with lymph node metastasis than patients without lymph node metastasis (P=0.005). Receiver's operating characteristic (ROC) curve analysis revealed that activation ratio of MMP-2 discriminate better than and activation ratio of MMP-9 between patients with and without lymph not le metastasis. Activation ratio of MMP-2 could predict risk of lymph node metastasis development in patients without lymph node involvement.Conclusion: The study concluded that activation of MMP-2 and MMP-9 was significantly higher in malignant tissues as compared to adjacent normal tissues. Further, activation ratio of MMP-2 was significantly elevated in patients with lymph node metastasis as compared to patients Without lymph node metastasis, which could predict risk of lymph node metastasis development in node negative patients. (C) 2005 Wiley-Liss, Inc.