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 con trol 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 carcinoma s. Expression of STR-3 and regulation by retinoids was assessed in fiv e human pancreatic carcinoma cell lines using western and northern blo tting as well as nuclear run on assays. Results-There was pronounced o verexpression of STR-3 in 17 of 21 (80.9%) pancreatic carcinoma specim ens. STR-3 expression was predominantly located in peritumourous strom al 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 e xpressed STR-3 mRNA and protein. Furthermore, retinoid treatment resul ts in a time and dose dependent inhibition of STR-3 protein expression . This inhibition seems to be post-transcriptional as neither STR-3 ge ne transcription nor mRNA steady state concentrations were affected by retinoids. Conclusions-STR-3 overexpression in stromal as well as epi thelial elements during pancreatic carcinogenesis might contribute to the aggressive local growth and metastasis of pancreatic cancer and ca n be therapeutically targeted by retinoids.