Gong Y L, Xu G M, Huang W D, Chen L B
Department of Medical Oncology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, P.R. China.
J Surg Oncol. 2000 Feb;73(2):95-9. doi: 10.1002/(sici)1096-9098(200002)73:2<95::aid-jso7>3.0.co;2-r.
The objective was to evaluate the potent role of matrix metalloproteinases(MMPs) and the tissue inhibitors of metalloproteinases(TIMPs) in processes leading to metastasis and local invasiveness of Chinese human ductal adenocarcinomas of the pancreas. We also evaluated a possible biological association between the gene expression and clinical manifestations.
Northern blot and in situ hybridization have shown MMP and TIMP gene expression in the pancreas and alterations associated with neoplastic transformation. Fifteen cases of surgical pancreatic specimens were examined, using cDNA probes to MMP2, MMP9, and TIMP1. Findings were correlated with the size of tumor section, CA19-9, pathological classification, thrombosis, and infiltration of capsule and lymphonoids.
Increased levels of the mRNA of MMP2, MMP9, and TIMP1 genes, MMP2 approximately MMP9<TIMP1, were found in pancreatic cancer tissues examined. Low levels of transcripts for MMP2, MMP9, and TIMP1 were detectable in pancreata of organ donors. Transcripts coding for MMP2, MMP9, and TIMP1 were found in both stroma and tumor cells. However, gene expression of MMP2, MMP9, and TIMP1 has shown an obvious correlation with the infiltration of capsule cells, surrounding lymphonoids and specific histopathological features.
We concluded that the imbalance between MMPs and TIMPs may help physicians to assess the metastatic potential and then tell the prognosis of individual patients.
本研究旨在评估基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)在中国胰腺癌导管腺癌转移和局部侵袭过程中的重要作用。我们还评估了基因表达与临床表现之间可能存在的生物学关联。
Northern印迹法和原位杂交法已显示MMP和TIMP基因在胰腺中的表达以及与肿瘤转化相关的改变。使用针对MMP2、MMP9和TIMP1的cDNA探针,对15例手术切除的胰腺标本进行检测。研究结果与肿瘤切片大小、CA19-9、病理分类、血栓形成以及包膜和淋巴结浸润情况相关联。
在所检测的胰腺癌组织中发现MMP2、MMP9和TIMP1基因的mRNA水平升高,MMP2约等于MMP9<TIMP1。在器官捐献者的胰腺中可检测到低水平的MMP2、MMP9和TIMP1转录本。在基质和肿瘤细胞中均发现了编码MMP2、MMP9和TIMP1的转录本。然而,MMP2、MMP9和TIMP1的基因表达与包膜细胞浸润、周围淋巴结以及特定组织病理学特征之间存在明显相关性。
我们得出结论,MMPs与TIMPs之间的失衡可能有助于医生评估转移潜能,进而判断个体患者的预后。