Limits...
Endostatin expression in pancreatic tissue is modulated by elastase.

Brammer RD, Bramhall SR, Eggo MC - Br. J. Cancer (2005)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, UK.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Western immunoblotting demonstrating the presence of endostatin-immunoreactive fragments in HBSS-soluble and SDS-soluble extracts from normal and cancer pancreas (N – normal pancreas, C – cancer pancreas).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2361736&req=5

fig1: Western immunoblotting demonstrating the presence of endostatin-immunoreactive fragments in HBSS-soluble and SDS-soluble extracts from normal and cancer pancreas (N – normal pancreas, C – cancer pancreas).

Mentions: Figure 1 shows a Western blot of extracts of proteins in the soluble fraction and the SDS-solubilised material from normal and cancerous pancreatic tissue, probed for endostatin. Immunoreactive bands are present at 120, 70, 36 and 20 kDa. The larger bands contain the endostatin fragment at their C terminus. The soluble fraction contains collagen XVIII (120 kDa), a 70 kDa fragment and the NC-1 fragment (36 kDa) in both normal pancreatic and pancreatic cancer tissue. The 20 kDa form of mature endostatin is present in the cancer tissue but not normal tissue. The SDS-solubilised fraction contains the 36 kDa fragment in both normal and pancreatic cancer tissue.


Endostatin expression in pancreatic tissue is modulated by elastase.

Brammer RD, Bramhall SR, Eggo MC - Br. J. Cancer (2005)

Western immunoblotting demonstrating the presence of endostatin-immunoreactive fragments in HBSS-soluble and SDS-soluble extracts from normal and cancer pancreas (N – normal pancreas, C – cancer pancreas).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361736&req=5

fig1: Western immunoblotting demonstrating the presence of endostatin-immunoreactive fragments in HBSS-soluble and SDS-soluble extracts from normal and cancer pancreas (N – normal pancreas, C – cancer pancreas).
Mentions: Figure 1 shows a Western blot of extracts of proteins in the soluble fraction and the SDS-solubilised material from normal and cancerous pancreatic tissue, probed for endostatin. Immunoreactive bands are present at 120, 70, 36 and 20 kDa. The larger bands contain the endostatin fragment at their C terminus. The soluble fraction contains collagen XVIII (120 kDa), a 70 kDa fragment and the NC-1 fragment (36 kDa) in both normal pancreatic and pancreatic cancer tissue. The 20 kDa form of mature endostatin is present in the cancer tissue but not normal tissue. The SDS-solubilised fraction contains the 36 kDa fragment in both normal and pancreatic cancer tissue.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, UK.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus