Department of Surgery, Klinikum rechts der Isar, Technische Universität München, München, Germany.
Int J Colorectal Dis. 2010 May;25(5):573-81. doi: 10.1007/s00384-010-0901-1. Epub 2010 Feb 17.
Chemotactic cytokines play a role in angiogenesis and attraction of immune cells. However, their contribution to tumor formation remains incompletely understood. In a previous transcriptome study, we identified a family of structurally related chemokines of the CXC-family to be specifically up-regulated in colorectal cancer. The aim of the present study was to investigate the regulation of their expression in colon cancer cells and to test the hypothesis that altered CXC-chemokine expression is related to critical clinical parameters, such as survival or metastasis formation.
Expression levels of interleukin-8 (CXCL-8) and growth-related oncogenes 2 and 3 (GRO-2/CXCL-2 and GRO-3/CXCL-3) were quantified using qRT-PCR in 97 patients with completely resected colon carcinoma and correlated with clinical parameters. Moreover, 16 samples of normal mucosa, nine samples of benign adenoma, and 11 samples of liver metastasis were analyzed. Next, the regulation of chemokine expression in response to various stimuli was tested in colon cancer cell lines (HT29, HCT116, CaCO2).
Expression of GRO-2, GRO-3, and IL-8 was significantly increased in colon cancer as compared to normal colon tissue. Expression of GRO-2 and GRO-3 was already enhanced in premalignant adenomas, and GRO-3 was significantly down-regulated in liver metastasis as compared to the primary tumor. Importantly, expression of GRO-3 was significantly higher in patients with local versus systemic disease. Moreover, IL-8 expression was significantly associated to overall post-operative survival. Finally, all chemokines were strongly induced by IL-1alpha in the colon cancer cell lines tested, indicating a potential link to inflammatory processes.
In accordance with earlier findings, we report here a significantly increased expression of GRO-2, GRO-3, and IL-8 in colon carcinoma as compared to normal tissue. Furthermore, GRO-3 was related to metastasis formation, and IL-8 was associated with survival, suggesting a potential predictive power of these markers.
趋化性细胞因子在血管生成和免疫细胞的吸引中发挥作用。然而，它们在肿瘤形成中的作用仍不完全清楚。在之前的转录组研究中，我们发现一组结构相关的 CXC 家族趋化因子在结直肠癌中特异性地上调。本研究的目的是研究结肠癌细胞中它们的表达调控，并检验假设，即改变的 CXC 趋化因子表达与关键的临床参数（如生存或转移形成）相关。
使用 qRT-PCR 定量检测 97 例完全切除的结肠癌患者中白细胞介素 8（CXCL-8）和生长相关癌基因 2 和 3（GRO-2/CXCL-2 和 GRO-3/CXCL-3）的表达水平，并与临床参数相关。此外，分析了 16 例正常黏膜、9 例良性腺瘤和 11 例肝转移样本。然后，在结肠癌细胞系（HT29、HCT116、CaCO2）中测试了对各种刺激的趋化因子表达的调节。
与正常结肠组织相比，GRO-2、GRO-3 和 IL-8 在结肠癌中的表达显著增加。在癌前腺瘤中 GRO-2 和 GRO-3 的表达已经增强，而 GRO-3 在肝转移中与原发肿瘤相比显著下调。重要的是，GRO-3 的表达在局部疾病患者中明显高于全身性疾病患者。此外，IL-8 的表达与总体术后生存显著相关。最后，所有趋化因子在测试的结肠癌细胞系中均被 IL-1alpha 强烈诱导，表明与炎症过程存在潜在联系。
与早期发现一致，我们在此报告与正常组织相比，GRO-2、GRO-3 和 IL-8 在结肠癌中的表达显著增加。此外，GRO-3 与转移形成有关，IL-8 与生存有关，提示这些标志物具有潜在的预测能力。
