Metalloproteinase 2 and 9 activity in the development of pancreatic cancer.
Metalloproteinase 2 and 9 activity in the development of pancreatic cancer.
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DOI：
10.2478/v10035-012-0064-6
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发表时间：
2012-08-01
期刊：
影响因子：
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通讯作者：
Gardian, Katarzyna
中科院分区：
文献类型：
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作者：
Durlik, Marek;Gardian, Katarzyna
未标记：胰腺癌是女性和男性的第四大常见癌症。在波兰，在过去的十年中，死于胰腺癌的人数增加了29%。本研究的目的是确定金属蛋白酶2和9的活性与胰腺癌的进展和侵袭性之间的关系。材料和方法：收集36例确诊的胰腺癌患者的组织标本，这些患者接受了Whiple手术。对肿瘤组织进行凝胶酶谱、原位酶谱和免疫组织化学分析。结果：MMPs的活性主要存在于癌细胞中。活动型MMP2(62 KDa)占88%，MMP9(83 KDa)占38%。相比之下，免疫组织化学染色显示所有研究组织中均有金属蛋白酶9的表达。根据肿瘤的组织学分级评估基质金属蛋白酶的活性。在G1组中，基质金属蛋白酶9无活性。通过比较活性，我们得出结论：分化程度最高的肿瘤中MMPs的活性明显低于G2和G3组。金属蛋白酶9的表达分析显示，不同组织成熟度的组间无显著差异。N0组和N1组MMP9表达水平无明显差异。结论：G1组MMP9活性缺失可能提示MMP9仅在较高级别的肿瘤中被激活。我们已经证明，在所有组织学级别中都发现了一种活性形式的MMP2，这支持它参与了胰腺癌的发展。金属蛋白酶是抗癌治疗的靶点，但不仅要考虑金属蛋白酶的表达水平，还要考虑它们的活性水平和与其活化相关的因素。
UNLABELLED: Pancreatic adenocarcinoma is the fourth most common cancer occurring in both women and men. In Poland, within the past ten years the number of deaths from pancreatic cancer increased by 29%.The aim of the study was to determine the correlation between the activity of metalloproteinase (MMP) 2 and 9 and progression and aggressiveness of pancreatic cancer.MATERIAL AND METHODS: Tissue samples were collected from 36 patients with diagnosed pancreatic adenocarcinoma who underwent Whipple resection. Tumor tissues were analyzed by gel zymography, zymography in situ and immunohistochemistry.RESULTS: The activity of MMPs was found mainly in cancer cells. Active form of MMP2 (62 kDa) was present in 88% of cases and MMP9 (83 kDa) in 38% of cases. By contrast, immunohistochemical staining revealed the presence of metalloproteinase 9 in all studied tissues. MMP activity was assessed against histological grade of the tumor. In the case of group G1 there was no activity of matrix metalloproteinase 9. By comparing the activity we concluded that the activity of MMPs in tumors with the highest degree of differentiation is significantly lower than in G2 and G3. Metalloproteinase 9 expression analysis revealed no significant differences between the groups of various degrees of histological maturity. The level of expression did not differ between the groups N0 and N1.CONCLUSION: Lack of metalloproteinase 9 activity in group G1 may indicate that MMP9 is activated only in higher tumor grades. We have shown that an active form of MMP2 is found in all histological grades, which supports its involvement in the development of pancreatic cancer. Metalloproteinases are attractive target of anticancer therapy but not only the level of expression of metalloproteinases should be taken into account but also their level of activity and factors associated with their activation.