Rega Institute for Medical Research, Laboratory of Molecular Immunology, K. U. Leuven, 3000 Leuven, Belgium.
Hum Pathol. 2010 Jul;41(7):990-1001. doi: 10.1016/j.humpath.2009.09.021. Epub 2010 Mar 23.
Chemokines influence tumor progression through regulation of leukocyte chemotaxis, angiogenesis, and metastasis. In this study, the regulated expression of angiogenic (stromal cell-derived factor [SDF]-1/CXCL12 and interleukin [IL]-8/CXCL8) and angiostatic (platelet factor [PF]-4var/CXCL4L1 and inducible protein [IP-10]/CXCL10) chemokines was examined in human colorectal and esophageal cancer. In HCT 116 and HCT-8 colorectal adenocarcinoma cells, the production of IL-8 immunoreactivity was up-regulated by IL-1beta, tumor necrosis factor (TNF)-alpha, the toll-like receptor (TLR) ligands double-stranded RNA and peptidoglycan and phorbol ester. Increased PF-4 and synergistic IL-8 and IP-10 induction in carcinoma cells after stimulation with IL-1beta plus TNF-alpha or interferon-gamma was demonstrated by enzyme-linked immunosorbent assay, quantitative reverse transcriptase polymerase chain reaction, or immunocytochemistry. In addition, IL-8 from HT-29 colorectal adenocarcinoma cells was molecularly identified as intact chemokine, as well as NH(2)-terminally truncated, more active IL-8(6-77). The presence of PF-4var, SDF-1, and vascular endothelial growth factor (VEGF) was evidenced by immunohistochemistry in surgical samples from 51 patients operated on for colon adenocarcinoma (AC), esophageal AC, or esophageal squamous cell carcinoma (SCC). PF-4var was strongly detected in colorectal cancer, whereas its expression in esophageal cancer was rather weak. Staining for SDF-1 was almost negative in esophageal SCC, whereas a more intense and frequent staining was observed in AC of the esophagus and colon. Staining for VEGF was moderately to strongly positive in all 3 types of cancer, although less prominent in esophageal AC. The heterogenous expression of angiogenic (IL-8, SDF-1) as well as angiostatic (IP-10, PF-4var) chemokines not only within the tumor and between the different cases but also between the different tumor cell types may indicate a distinct role of the various chemokines in the complex process of tumor development.
趋化因子通过调节白细胞趋化性、血管生成和转移来影响肿瘤的进展。在这项研究中，研究了人结直肠癌和食管癌中血管生成（基质细胞衍生因子[SDF]-1/CXCL12 和白细胞介素[IL]-8/CXCL8）和血管生成抑制（血小板因子[PF]-4var/CXCL4L1 和诱导蛋白[IP-10]/CXCL10）趋化因子的调节表达。在 HCT 116 和 HCT-8 结直肠腺癌细胞中，IL-1β、肿瘤坏死因子（TNF）-α、Toll 样受体（TLR）配体双链 RNA 和肽聚糖以及佛波酯上调了 IL-8 免疫反应性的产生。通过酶联免疫吸附试验、定量逆转录聚合酶链反应或免疫细胞化学证实，用 IL-1β加 TNF-α或干扰素-γ刺激后，癌细胞中 PF-4 和协同的 IL-8 和 IP-10 诱导增加。此外，HT-29 结直肠腺癌细胞中的 IL-8 被鉴定为完整的趋化因子，以及 NH2 末端截断的、更活跃的 IL-8(6-77)。在 51 例接受结肠癌（AC）、食管癌 AC 或食管鳞状细胞癌（SCC）手术的患者的手术样本中，通过免疫组织化学检测到 PF-4var、SDF-1 和血管内皮生长因子（VEGF）的存在。PF-4var 在结直肠癌中强烈表达，而在食管癌中表达较弱。食管 SCC 中 SDF-1 的染色几乎为阴性，而食管和结肠的 AC 中观察到更强烈和更频繁的染色。所有 3 种类型的癌症中 VEGF 的染色均为中度至强阳性，尽管在食管 AC 中不太明显。在肿瘤内和不同病例之间以及不同肿瘤细胞类型之间，血管生成（IL-8、SDF-1）和血管生成抑制（IP-10、PF-4var）趋化因子的异质性表达不仅表明各种趋化因子在肿瘤发展的复杂过程中可能具有不同的作用。
