Brammer R D, Bramhall S R, Eggo M C
Division of Medical Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Br J Cancer. 2005 Jan 17;92(1):89-93. doi: 10.1038/sj.bjc.6602234.
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.
胰腺肿瘤是硬癌性、无血管的肿瘤，这表明它们可能产生血管生成抑制剂，抑制肿瘤及其转移灶的血管生成。我们在正常胰腺组织和癌组织中寻找血管生成抑制剂内皮抑素的证据。通过蛋白质免疫印迹法，我们发现癌组织中有成熟的20 kDa内皮抑素，而正常组织中没有。两种组织中均存在几种较高分子量的内皮抑素相关肽。正常组织提取物能够降解外源性内皮抑素，而癌组织提取物则无此作用。尽管外分泌胰腺分泌无活性的胰蛋白酶、糜蛋白酶和弹性蛋白酶原，但我们研究了它们在这种降解过程中可能发挥的作用。胰蛋白酶/糜蛋白酶抑制剂大豆并未阻止正常胰腺提取物对内皮抑素的降解，但弹性蛋白酶特异性抑制剂弹性蛋白酶抑制剂降低了降解速率。胰腺肿瘤提取物未表现出任何可检测到的弹性蛋白酶活性，但正常胰腺提取物表达一种弹性蛋白酶（Km为1.1 mM）。我们得出结论，内皮抑素存在于胰腺癌组织中且稳定，这可能解释了它们无血管的性质，但正常胰腺组织表达包括弹性蛋白酶在内的酶，这些酶能迅速降解内皮抑素。内皮抑素的稳定性可能对其治疗用途有影响。
