von Marschall Z, Riecken E O, Rosewicz S
Department of Gastroenterology, Klinikum Benjamin Franklin, Berlin, Germany.
Gut. 1998 Nov;43(5):692-8. doi: 10.1136/gut.43.5.692.
Matrix metalloproteinases play an important role in the control of local tumour growth and metastasis of human pancreatic cancer.
To examine expression of recently discovered stromelysin 3 (STR-3) in human pancreatic cancer and pancreatic carcinoma cell lines and to investigate their regulation by retinoids.
STR-3 expression was examined by immunohistochemistry in 21 human pancreatic carcinomas. Expression of STR-3 and regulation by retinoids was assessed in five human pancreatic carcinoma cell lines using western and northern blotting as well as nuclear run on assays.
There was pronounced overexpression of STR-3 in 17 of 21 (80.9%) pancreatic carcinoma specimens. STR-3 expression was predominantly located in peritumourous stromal cells. Six of 21 (28.5%) carcinomas also revealed STR-3 expression in epithelial tumour cells whereas no STR-3 expression was observed in non-transformed pancreas. All five pancreatic carcinoma cell lines expressed STR-3 mRNA and protein. Furthermore, retinoid treatment results in a time and dose dependent inhibition of STR-3 protein expression. This inhibition seems to be post-transcriptional as neither STR-3 gene transcription nor mRNA steady state concentrations were affected by retinoids.
STR-3 overexpression in stromal as well as epithelial elements during pancreatic carcinogenesis might contribute to the aggressive local growth and metastasis of pancreatic cancer and can be therapeutically targeted by retinoids.
基质金属蛋白酶在人类胰腺癌的局部肿瘤生长和转移控制中发挥重要作用。
检测新发现的基质溶解素3（STR-3）在人类胰腺癌及胰腺癌细胞系中的表达，并研究其受维甲酸的调控情况。
采用免疫组织化学法检测21例人类胰腺癌组织中STR-3的表达。利用蛋白质印迹法、Northern印迹法以及核转录分析评估5种人类胰腺癌细胞系中STR-3的表达及其受维甲酸的调控。
21例胰腺癌标本中有17例（80.9%）出现STR-3明显过表达。STR-3表达主要位于肿瘤周围的基质细胞。21例中有6例（28.5%）癌组织的上皮肿瘤细胞也有STR-3表达，而在未转化的胰腺组织中未观察到STR-3表达。所有5种胰腺癌细胞系均表达STR-3 mRNA和蛋白。此外，维甲酸处理导致STR-3蛋白表达呈时间和剂量依赖性抑制。这种抑制似乎是转录后水平的，因为维甲酸既不影响STR-3基因转录，也不影响mRNA的稳态浓度。
胰腺癌发生过程中基质及上皮成分中STR-3的过表达可能有助于胰腺癌的侵袭性局部生长和转移，并且维甲酸可将其作为治疗靶点。
