Ohlund D, Lundin C, Ardnor B, Oman M, Naredi P, Sund M
Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
Br J Cancer. 2009 Jul 7;101(1):91-7. doi: 10.1038/sj.bjc.6605107. Epub 2009 Jun 2.
Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients.
The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques.
Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival.
Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.
尽管近年来手术和肿瘤治疗取得了进展，但胰腺癌仍是一种可怕的疾病，死亡率很高。该领域因缺乏用于患者随访的良好预后和预测性肿瘤生物标志物而受到阻碍。
通过酶联免疫吸附测定法（ELISA）测量胰腺癌患者和对照组中IV型胶原蛋白的循环水平。采用免疫荧光和蛋白质印迹技术研究IV型胶原蛋白在正常胰腺、胰腺癌组织和胰腺癌细胞系中的表达模式。
胰腺癌患者的IV型胶原蛋白循环水平显著升高。在胰腺癌组织中，肿瘤基质中靠近癌细胞处发现高水平的IV型胶原蛋白表达。此外，发现胰腺癌细胞在体外产生并分泌IV型胶原蛋白，这在一定程度上可以解释在胰腺癌组织中观察到的IV型胶原蛋白高表达以及胰腺癌患者循环水平的升高。具有临床重要性的是，我们的结果表明，手术后IV型胶原蛋白的循环水平与接受根治性胰十二指肠切除术治疗的胰腺癌患者的预后密切相关。术后持续高水平的循环IV型胶原蛋白表明疾病快速复发且生存率低。
我们的结果最重要的是表明，与基质相关的物质可作为潜在的癌症生物标志物进行评估，从而强调了肿瘤微环境在这方面的重要性。
