Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials.
Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials.
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发表时间：
2001-10
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通讯作者：
Aihua Li;M. Varney;Rakesh K. Singh
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作者：
Aihua Li;M. Varney;Rakesh K. Singh
本研究检测了多功能细胞因子白细胞介素8（IL-8）及其受体CXCR 1和CXCR 2在不同转移潜能的人结肠癌细胞中的表达，并确定了它们在调节转移相关表型中的作用。实验设计IL-8，CXCR 1，和CXCR 2蛋白和mRNA的表达，采用ELISA，免疫细胞化学和逆转录-PCR检测在人结肠癌细胞具有不同的转移潜力。分析IL-8介导的增殖、迁移和肿瘤-内皮细胞相互作用。结果IL-8 mRNA和蛋白在Caco 2细胞中表达较低，在KM 12 C细胞中表达升高，在KM 12 L4细胞中表达升高，提示IL-8的产生与肿瘤的转移潜能有关。类似地，CXCR 1和CXCR 2在Caco 2细胞中的表达低于低和高转移性KM 12 C和KM 12 L4细胞。重组人IL-8对结肠癌细胞增殖有促进作用。此外，表达不同水平IL-8的低和高转移性细胞的增殖被IL-8、CXCR 1和CXCR 2的中和抗体抑制。我们观察到表达不同水平IL-8的结肠癌细胞的侵袭潜力存在显着差异。此外，我们观察到IL-8以自分泌和旁分泌方式调节肿瘤细胞与内皮细胞的粘附。结论IL-8的组成性表达与人结肠癌细胞的侵袭性有关，IL-8可能在调节与进展和转移相关的不同转移表型中发挥作用。
PURPOSE In the present study, we examined the expression of a multifunctional cytokine, interleukin 8 (IL-8), and its receptors, CXCR1 and CXCR2, in human colon carcinoma cells with different metastatic potentials and determined their role in modulating phenotypes associated with metastasis. EXPERIMENTAL DESIGN IL-8, CXCR1, and CXCR2 protein and mRNA expression were examined using ELISA, immunocytochemistry, and reverse transcription-PCR in human colon carcinoma cells with different metastatic potentials. IL-8-mediated proliferation, migration, and tumor-endothelial cell interaction were analyzed. RESULTS IL-8 mRNA and protein expression was very low in Caco2 cells but elevated in KM12C cells and very high in KM12L4 cells, suggesting an association between the IL-8 production and metastatic potential. Similarly, CXCR1 and CXCR2 expression was lower in Caco2 cells than in low and high metastatic KM12C and KM12L4 cells. The recombinant human IL-8 enhanced the proliferation of colon carcinoma cells. Furthermore, proliferation of low and high metastatic cells expressing different levels of IL-8 was inhibited by neutralizing antibodies to IL-8, CXCR1, and CXCR2. We observed significant differences in the invasive potential of colon carcinoma cells expressing different levels of IL-8. In addition, we observed that IL-8 modulates adhesion of tumor cells to endothelial cells in an autocrine and paracrine manner. CONCLUSION Our present data suggest an association between constitutive expression of IL-8 and aggressiveness in human colon carcinoma cells and the possible role of IL-8 in modulating different metastatic phenotypes associated with progression and metastasis.