Cahlin Christian, Lönnroth Christina, Arvidsson Annette, Nordgren Svante, Lundholm Kent
Department of Surgery, Surgical Metabolic Research Laboratory at Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg, Sweden.
Int J Oncol. 2008 Apr;32(4):909-18.
Connections among specific proteins (Bax, Bcl-2, bFGF, COX-1, COX-2, E-cad, p15, p53, PCNA, TGFbeta3, TUNEL, vWF) in control of cell proliferation, apoptosis, cell adhesion, tumor vascularity and PGE2 content were evaluated in colon cancer as related to disease progression and survival. Tumor tissue and adjacent normal colon mucosa were obtained at curative resection in 22 patients. PGE2 concentrations were assessed in tumor tissue and tumor derived blood, splanchnic blood, peripheral venous blood and urine. Host inflammation was determined (CRP, ESR) in relationship to tumor differentiation and stage. Patients survived as expected according to Dukes A-D staging. Growth-related proteins correlated between tumor cells and stroma as well as between protein factors within tumor cells and tumor stroma. COX-2 predicted tumor tissue content of PGE2 (p<0.002), without reflection in tumor derived blood. Systemic inflammation was predicted by p15, TGFbeta3 and Bcl-2 in tumor tissue (p<0.001). p15 and vWF predicted reduced survival in ungrouped patients (p<0.02), while p15, PCNA, TGFbeta3 and vWF predicted reduced survival (p<0.0001) when patient grouping accounted for high tumor content of PGE2. Our results connect systemic inflammation and survival to COX-2 staining and increased PGE2 in colon cancer. Thus, it seems important to understand proximal signals behind upregulation of COX-2 and subsequent PGE2 production in certain tumor cells in colon cancer.
在结肠癌中，评估了特定蛋白质（Bax、Bcl-2、碱性成纤维细胞生长因子、环氧化酶-1、环氧化酶-2、E-钙黏蛋白、p15、p53、增殖细胞核抗原、转化生长因子β3、脱氧核糖核苷酸末端转移酶介导的缺口末端标记、血管性血友病因子）之间在控制细胞增殖、凋亡、细胞黏附、肿瘤血管生成和前列腺素E2含量方面的联系，这些联系与疾病进展和生存相关。在22例患者进行根治性切除时获取肿瘤组织和相邻的正常结肠黏膜。评估肿瘤组织、肿瘤来源血液、内脏血液、外周静脉血和尿液中的前列腺素E2浓度。确定宿主炎症（C反应蛋白、红细胞沉降率）与肿瘤分化和分期的关系。患者的生存情况符合预期的Dukes A-D分期。生长相关蛋白在肿瘤细胞与基质之间以及肿瘤细胞内的蛋白因子与肿瘤基质之间存在相关性。环氧化酶-2可预测肿瘤组织中前列腺素E2的含量（p<0.002），但在肿瘤来源血液中未体现。肿瘤组织中的p15、转化生长因子β3和Bcl-2可预测全身炎症（p<0.001）。p15和血管性血友病因子可预测未分组患者的生存率降低（p<0.02），而当患者分组考虑到前列腺素E2含量高的肿瘤时，p15、增殖细胞核抗原、转化生长因子β3和血管性血友病因子可预测生存率降低（p<0.0001）。我们的结果将全身炎症和生存与结肠癌中环氧化酶-2染色及前列腺素E2增加联系起来。因此，了解结肠癌某些肿瘤细胞中环氧化酶-2上调及随后前列腺素E2产生背后的近端信号似乎很重要。
