Bramhall S R, Neoptolemos J P, Stamp G W, Lemoine N R
Department of Surgery, City Hospital NHS Trust, Birmingham, U.K.
J Pathol. 1997 Jul;182(3):347-55. doi: 10.1002/(SICI)1096-9896(199707)182:3<347::AID-PATH848>3.0.CO;2-J.
Degradation of the extracellular matrix (ECM) is an essential step in tumour invasion and metastasis. The matrix metalloproteinases (MMPs) each have different substrate specificities within the ECM and are important in its degradation. MMP activity is dependent on the levels of activated MMP and tissue inhibitors of matrix metalloproteinases (TIMPs). The expression of MMPs and TIMPs in pancreatic carcinoma, normal pancreas, and pancreatic carcinoma cell lines has been determined by Northern analysis. The transcripts have been localized by in situ hybridization and the MMP2 protein by immunohistochemistry. Expression of MMP2, -7, and -11 was greater in pancreatic carcinoma than in normal pancreas (P < 0.01). MMP7 expression in normal pancreas and MMP7 and -11 expression in tumours was always seen the TIMP1 expression. TIMP2 was expressed in only half of the tumours and a previously undescribed transcript size is reported for TIMP2. MTMMP was expressed concurrently with MMP2 in 64 per cent of tumours, but concurrent MMP2 and TIMP2 expression occurred in only half. MMP2 mRNA was found more often in the tumour stroma than with the other MMPs or TIMPs (P < 0.02). It is concluded that while overexpression of MMP7 and -11 may be countered by TIMP1, the aggressive phenotype of pancreatic carcinoma may occur because of overexpression of MMP2, activated by MTMMP and associated with a reduced expression of TIMP2.
细胞外基质（ECM）的降解是肿瘤侵袭和转移的关键步骤。基质金属蛋白酶（MMPs）在ECM中各自具有不同的底物特异性，对其降解起重要作用。MMP活性取决于活化的MMP水平和基质金属蛋白酶组织抑制剂（TIMPs）。通过Northern分析确定了MMPs和TIMPs在胰腺癌、正常胰腺及胰腺癌细胞系中的表达。通过原位杂交对转录本进行定位，通过免疫组织化学对MMP2蛋白进行定位。MMP2、-7和-11在胰腺癌中的表达高于正常胰腺（P < 0.01）。正常胰腺中MMP7的表达以及肿瘤中MMP7和-11的表达总是与TIMP1的表达相关。仅一半的肿瘤中表达TIMP2，且报道了一种先前未描述的TIMP2转录本大小。在64%的肿瘤中，MTMMP与MMP2同时表达，但同时表达MMP2和TIMP2的情况仅占一半。与其他MMPs或TIMPs相比，MMP2 mRNA在肿瘤基质中更常见（P < 0.02）。结论是，虽然MMP7和-11的过表达可能被TIMP1抵消，但胰腺癌的侵袭性表型可能是由于MMP2的过表达所致，MMP2由MTMMP激活并与TIMP2表达降低相关。
