Durlik Marek, Gardian Katarzyna
Department of Surgical Research and Transplantology, Medical Research Centre Polish Academy of Sciences in Warsaw Ministry of the Internal Affairs in Warsaw.
Pol Przegl Chir. 2012 Aug;84(8):377-82. doi: 10.2478/v10035-012-0064-6.
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.
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.
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.
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.
胰腺腺癌是男性和女性中第四大常见癌症。在波兰，过去十年间胰腺癌死亡人数增加了29%。本研究的目的是确定金属蛋白酶（MMP）2和9的活性与胰腺癌进展及侵袭性之间的相关性。
从36例接受胰十二指肠切除术的确诊胰腺腺癌患者中采集组织样本。通过凝胶酶谱法、原位酶谱法和免疫组织化学对肿瘤组织进行分析。
MMPs的活性主要在癌细胞中发现。活性形式的MMP2（62 kDa）在88%的病例中存在，MMP9（83 kDa）在38%的病例中存在。相比之下，免疫组织化学染色显示在所有研究组织中均存在金属蛋白酶9。根据肿瘤的组织学分级评估MMP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的活性显著低于G2和G3组。金属蛋白酶9表达分析显示不同程度组织学成熟度的组间无显著差异。N0组和N1组之间的表达水平无差异。
G1组中缺乏金属蛋白酶9活性可能表明MMP9仅在较高肿瘤分级中被激活。我们已经表明，在所有组织学分级中均发现活性形式的MMP2，这支持了其参与胰腺癌的发展。金属蛋白酶是抗癌治疗的有吸引力的靶点，但不仅应考虑金属蛋白酶的表达水平，还应考虑其活性水平以及与其激活相关的因素。
