Z. Vonmarschall et al., STROMELYSIN-3 IS OVEREXPRESSED IN HUMAN PANCREATIC-CARCINOMA AND REGULATED BY RETINOIC ACID IN PANCREATIC-CARCINOMA CELL-LINES, Gut, 43(5), 1998, pp. 692-698
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.