Endostatin expression in pancreatic tissue is modulated by elastase.
Pancreatic tumours are scirrhous, avascular tumours, suggesting that they may produce angiogenesis inhibitors that suppress the growth of the vasculature to the tumour and metastases. We have sought evidence for the angiogenesis inhibitor, endostatin, in normal and cancerous pancreatic tissue. Using Western blotting, we found mature 20 kDa endostatin in cancer tissue but not in normal tissue. Several endostatin-related peptides of higher mol wt were present in both tissues. Extracts from normal tissue were able to degrade exogenous endostatin, whereas extracts from cancer were without effect. Although the exocrine pancreas secretes inactive proenzymes of trypsin, chymotrypsin and elastase, their possible role in this degradation was examined. The trypsin/chymotrypsin inhibitor, Glycine max, did not prevent the degradation of endostatin by normal pancreatic extracts but elastatinal, a specific inhibitor of elastase, reduced the rate of degradation. Extracts of pancreatic tumours did not express any detectable elastase activity, but an elastase (Km 1.1 mM) was expressed by extracts of normal pancreas. We conclude that endostatin is present and stable in pancreatic cancer tissues, which may explain their avascular nature, but that normal pancreatic tissue expresses enzymes, including elastase, which rapidly degrade endostatin. The stability of endostatin may have implications for its therapeutic use.
Brammer
R D
RD
Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Bramhall
S R
SR
Eggo
M C
MC
D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D015153:Blotting, Western; D043170:Collagen Type XVIII / Q000378:metabolism; D043169:Endostatins / Q000378:metabolism*; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D010196:Pancreatic Elastase