Stromelysin 3 is overexpressed in human pancreatic carcinoma and regulated by retinoic acid in pancreatic carcinoma cell lines

被引:35
作者
von Marschall, Z [1 ]
Riecken, EO [1 ]
Rosewicz, S [1 ]
机构
[1] Free Univ Berlin, Klinikum Benjamin Franklin, Dept Gastroenterol, Med Klin 1, D-12200 Berlin, Germany
关键词
matrix metalloproteinases; pancreatic cancer; stromelysin; 3; retinoic acid;
D O I
10.1136/gut.43.5.692
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background-Matrix metalloproteinases play an important role in the control of local tumour growth and metastasis of human pancreatic cancer. Aims-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. Methods-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. Results-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. Conclusions-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.
引用
收藏
页码:692 / 698
页数:7
相关论文
共 30 条
[1]  
ANDERSON IC, 1995, CANCER RES, V55, P4120
[2]  
[Anonymous], PANCREAS BIOL PATHOB
[3]   CHEMOTHERAPY FOR PANCREATIC-CANCER [J].
ARBUCK, SG .
BAILLIERES CLINICAL GASTROENTEROLOGY, 1990, 4 (04) :953-968
[4]   CARCINOMA OF THE PANCREAS AND PAPILLA OF VATER - PRESENTING SYMPTOMS, SIGNS, AND DIAGNOSIS RELATED TO STAGE AND TUMOR SITE - A PROSPECTIVE MULTICENTER TRIAL IN 472 PATIENTS [J].
BAKKEVOLD, KE ;
ARNESJO, B ;
KAMBESTAD, B .
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1992, 27 (04) :317-325
[5]   A NOVEL METALLOPROTEINASE GENE SPECIFICALLY EXPRESSED IN STROMAL CELLS OF BREAST CARCINOMAS [J].
BASSET, P ;
BELLOCQ, JP ;
WOLF, C ;
STOLL, I ;
HUTIN, P ;
LIMACHER, JM ;
PODHAJCER, OL ;
CHENARD, MP ;
RIO, MC ;
CHAMBON, P .
NATURE, 1990, 348 (6303) :699-704
[6]  
Chen Wen-Tien, 1992, Current Opinion in Cell Biology, V4, P802
[7]   ISOLATION OF BIOLOGICALLY-ACTIVE RIBONUCLEIC-ACID FROM SOURCES ENRICHED IN RIBONUCLEASE [J].
CHIRGWIN, JM ;
PRZYBYLA, AE ;
MACDONALD, RJ ;
RUTTER, WJ .
BIOCHEMISTRY, 1979, 18 (24) :5294-5299
[8]   CORRELATION BETWEEN STROMELYSIN-3 MESSENGER-RNA LEVEL AND OUTCOME OF HUMAN BREAST-CANCER [J].
ENGEL, G ;
HESELMEYER, K ;
AUER, G ;
BACKDAHL, M ;
ERIKSSON, E ;
LINDER, S .
INTERNATIONAL JOURNAL OF CANCER, 1994, 58 (06) :830-835
[9]   ALPHA(1)-ANTITRYPSIN-INDEPENDENT AND ANCHORAGE-INDEPENDENT GROWTH OF MCF-7 BREAST-CANCER CELLS [J].
FINLAY, TH ;
TAMIR, S ;
KADNER, SS ;
CRUZ, MR ;
YAVELOW, J ;
LEVITZ, M .
ENDOCRINOLOGY, 1993, 133 (03) :996-1102
[10]   RETINOIC ACID RECEPTORS AND CELLULAR RETINOID-BINDING PROTEINS - COMPLEX INTERPLAY IN RETINOID SIGNALING [J].
GIGUERE, V .
ENDOCRINE REVIEWS, 1994, 15 (01) :61-79