Stromal cell-derived factor-1 promotes cell migration and tumor growth of colorectal metastasis
Stromal cell-derived factor-1 promotes cell migration and tumor growth of colorectal metastasis
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DOI：
10.1593/neo.07559
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发表时间：
2007-10-01
期刊：
影响因子：
4.8
通讯作者：
Menger, Michael D.
中科院分区：
文献类型：
--
作者：
Kollmar, Otto;Rupertus, Kathrin;Menger, Michael D.
在一个已建立的结直肠癌肝外转移小鼠模型中，我们分析了基质细胞衍生因子（SDF）1是否在体外刺激肿瘤细胞迁移以及在体内刺激血管生成和肿瘤生长。
方法：利用趋化室，研究了不同浓度的SDF - 1刺激下CT26.WT结直肠肿瘤细胞的迁移情况。为了评估体内血管生成和肿瘤生长情况，将转染绿色荧光蛋白的CT26.WT细胞植入同基因BALB/c小鼠的背部皮褶腔室中。5天后，在肿瘤局部给予SDF - 1。在接下来的9天里，利用活体荧光显微镜、组织学和免疫组织化学方法研究细胞增殖、肿瘤微血管形成和生长情况。仅用磷酸盐缓冲液（PBS）处理的肿瘤作为对照。
结果：在体外，超过30%未受刺激的CT26.WT细胞表达SDF - 1受体CXCR4。在趋化实验中，SDF - 1引起细胞迁移呈剂量依赖性增加。在体内，SDF - 1加速新生血管形成，并导致肿瘤生长显著增加。经SDF - 1处理的肿瘤毛细血管显著扩张。有趣的是，SDF - 1处理与增殖细胞核抗原表达显著增加以及裂解的半胱天冬酶 - 3下调相关。
结论：我们的研究表明，CXC趋化因子SDF - 1在体外促进肿瘤细胞迁移，在体内由于血管生成依赖性诱导肿瘤细胞增殖和抑制凋亡细胞死亡，从而促进已建立的肝外转移肿瘤的生长。
In a mouse model of established extrahepatic colorectal metastasis, we analyzed whether stromal cell derived factor (SDF) 1 stimulates tumor cell migration in vitro and angiogenesis and tumor growth in vivo. Methods: Using chemotaxis chambers, CT26. WT colorectal tumor cell migration was studied under stimulation with different concentrations of SDF-1. To evaluate angiogenesis and tumor growth in vivo, green fluorescent protein-transfected CT26. WT cells were implanted in dorsal skinfold chambers of syngeneic BALB/ c mice. After 5 days, tumors were locally exposed to SDF-1. Cell proliferation, tumor microvascularization, and growth were studied during a further 9-day period using intravital fluorescence microscopy, histology, and immunohistochemistry. Tumors exposed to PBS only served as controls. Results: In vitro, > 30% of unstimulated CT26. WT cells showed expression of the SDF-1 receptor CXCR4. On chemotaxis assay, SDF-1 provoked a dose-dependent increase in cell migration. In vivo, SDF-1 accelerated neovascularization and induced a significant increase in tumor growth. Capillaries of SDF-1-treated tumors showed significant dilation. Of interest, SDF-1 treatment was associated with a significantly increased expression of proliferating cell nuclear antigen and a downregulation of cleaved caspase-3. Conclusion: Our study indicates that the CXC chemokine SDF-1 promotes tumor cell migration in vitro and tumor growth of established extrahepatic metastasis in vivo due to angiogenesis-dependent induction of tumor cell proliferation and inhibition of apoptotic cell death.