Ohlund Daniel, Ardnor Bjarne, Oman Mikael, Naredi Peter, Sund Malin
Department of Surgery, Umeå University Hospital, SE Umeå, Sweden.
Int J Cancer. 2008 Jun 15;122(12):2805-10. doi: 10.1002/ijc.23468.
Endostatin is a potent inhibitor of angiogenesis that is cleaved from the basement membrane protein type XVIII collagen. Expression of endostatin has recently been shown by Western blot analysis of tissue lysates in normal pancreas and pancreas cancer tissue. We show here that the expression pattern of type XVIII collagen/endostatin is shifted from a general basement membrane staining and is mainly located in the vasculature during tumor progression. This shift in type XVIII collagen/endostatin expression pattern coincides with an up-regulation of MMPs involved in endostatin processing in the tumor microenvironment, such as MMP-3, MMP-9 and MMP-13. The circulating levels of endostatin was analyzed in patients with pancreas cancer and compared to that of healthy controls, as well as after surgical treatment or in a group of nonoperable patients after intraperitoneal fluorouracil (5-FU) chemotherapy. The results show that patients with pancreas cancer have increased circulating levels of endostatin and that these levels are normalized after surgery or intraperitoneal chemotherapy. These findings indicate that endostatin could be used as a biomarker for pancreas cancer progression.
内皮抑素是一种从 XVIII 型胶原蛋白这种基底膜蛋白裂解而来的强效血管生成抑制剂。最近通过对正常胰腺组织和胰腺癌组织的裂解物进行蛋白质免疫印迹分析，证实了内皮抑素的表达。我们在此表明，XVIII 型胶原蛋白/内皮抑素的表达模式从一般的基底膜染色转变，在肿瘤进展过程中主要定位于脉管系统。XVIII 型胶原蛋白/内皮抑素表达模式的这种转变与肿瘤微环境中参与内皮抑素加工的基质金属蛋白酶（MMPs）的上调相一致，如 MMP-3、MMP-9 和 MMP-13。分析了胰腺癌患者体内内皮抑素的循环水平，并与健康对照者进行比较，同时也在手术治疗后或一组接受腹腔内氟尿嘧啶（5-FU）化疗的不可手术患者中进行了比较。结果显示，胰腺癌患者体内内皮抑素的循环水平升高，而这些水平在手术后或腹腔内化疗后恢复正常。这些发现表明内皮抑素可作为胰腺癌进展的生物标志物。
