Stromelysin 3 is overexpressed in human pancreatic carcinoma and regulated by retinoic acid in pancreatic carcinoma cell lines.
BACKGROUND
Matrix metalloproteinases play an important role in the control of local tumour growth and metastasis of human pancreatic cancer.


OBJECTIVE
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.
von Marschall
Z
Z
Department of Gastroenterology, Klinikum Benjamin Franklin, Berlin, Germany.
Riecken
E O
EO
Rosewicz
S
S
D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D014212:Tretinoin; D053507:Matrix Metalloproteinase 11; D008666:Metalloendopeptidases