EXPRESSION AND IN-SITU LOCALIZATION OF GENES-CODING FOR EXTRACELLULAR-MATRIX PROTEINS AND EXTRACELLULAR-MATRIX DEGRADING PROTEASES IN PANCREATIC-CANCER
EXPRESSION AND IN-SITU LOCALIZATION OF GENES-CODING FOR EXTRACELLULAR-MATRIX PROTEINS AND EXTRACELLULAR-MATRIX DEGRADING PROTEASES IN PANCREATIC-CANCER
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DOI：
10.1002/ijc.2910620409
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发表时间：
1995-08-09
影响因子：
6.4
通讯作者：
ADLER, G
中科院分区：
文献类型：
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作者：
GRESS, TM;MULLERPILLASCH, F;ADLER, G
胰腺癌表现出强烈的促结缔组织增生反应，其特征是间质结缔组织（I型和III型胶原，纤连蛋白）显著增生。在这项研究中，我们分析了编码细胞外基质成分（胶原蛋白I，III和IV，层粘连蛋白，纤连蛋白），细胞外基质降解金属蛋白酶（MMP-1，-2，-3和-9）和金属蛋白酶的组织抑制剂（TIMP-1和-2）的mRNA在胰腺癌和对照胰腺组织中的表达平衡，通过Northern印迹分析和mRNA原位杂交。MMP-1（间质胶原酶）和MMP-3（基质溶解素-1）的转录在胰腺癌和对照组织中未检测到。与对照胰腺组织相比，大多数胰腺癌组织样本中编码细胞外基质蛋白MMP-2（72-kDa IV型胶原酶）、MMP-9（92-kDa IV型胶原酶）、TIMP-1和TIMP-2的转录物的稳态水平升高。一个很好的相关性，这些MMPs和TIMPs的过度表达和稳态水平的转录编码细胞外基质蛋白，胶原蛋白的量和结缔组织增生反应的严重程度。原位杂交研究定位转录编码胶原I型和III型梭形基质细胞，而转录MMP-2，MMP-9，TIMP-1和TIMP-2，发现在基质和肿瘤细胞。MMP-2在间质细胞中表达量较高，TIMP-1和TIMP-2在肿瘤细胞和间质细胞中分布均匀，MMP-9在肿瘤细胞中表达相对较多。我们的结论是，在人类胰腺癌中，MMP-2，MMP-9，TIMP-1和TIMP-2可能参与导致这些肿瘤中观察到的强烈促纤维增生反应的过程。间质细胞和肿瘤细胞似乎都是人胰腺癌中MMPs和TIMPs的来源。(C)1995 Wiley-Liss，Inc.
Pancreatic cancer shows a strong desmoplastic reaction characterized by a remarkable proliferation of interstitial connective tissue (collagens type I and III, fibronectin). In this study we have analyzed the balance of expression of mRNAs encoding extracellular matrix components (collagens I, III and IV, laminin, fibronectin), extracellular matrix-degrading metalloproteinases (MMP-1, -2, -3 and -9) and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in pancreatic cancer and control pancreatic tissue by Northern-blot analysis and mRNA in site hybridization. Transcripts for MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) were not detectable in pancreatic cancer and control tissues. Steady-state levels of transcripts encoding extracellular matrix proteins, MMP-2 (72-kDa collagenase IV), MMP-9 (92-kDa collagenase type IV), TIMP-1 and TIMP-2 were elevated in the majority of pancreatic-cancer tissue samples as compared to control pancreatic tissue. A good correlation was seen between overexpression of these MMPs and TIMPs and the steady-state levels of transcripts coding for extracellular matrix proteins, the amount of collagen protein and the severity of the desmoplastic reaction. In situ hybridization studies localized transcripts coding for collagens type I and III to spindle-shaped stromal cells, whereas transcripts for MMP-2, MMP-9, TIMP-1 and TIMP-2, were found in both stromal and tumor cells. However, MMP-2 transcripts appeared to be more abundant in stromal cells, TIMP-1 and TIMP-2 transcripts were evenly distributed over tumor and stromal cells and relatively more MMP-9 transcripts were found in tumor cells. We conclude that, in human pancreatic cancer, MMP-2, MMP-9, TIMP-1 and TIMP-2 may be involved in processes leading to the strong desmoplastic reaction observed in these tumors. Both stromal and tumor cells appear to be the source of MMPs and TIMPs in human pancreatic cancer. (C) 1995 Wiley-Liss, Inc.