VEGFR1阳性造血祖细胞簇与人大肠癌转移的关系

Role of vascular endothelial growth factor receptor 1-positive hematopoietic progenitor cell clusters in human colorectal carcinoma metastasis

目的观察血管内皮生长因子受体1(VEGFR1)阳性造血祖细胞与人大肠癌转移的关系及机制。方法将人大肠癌细胞株SW480/M5瘤块原位接种至裸鼠结肠,建立大肠癌原位移植肝转移裸鼠模型,应用FCM观察转移灶内VEGFR1阳性造血祖细胞与大肠癌细胞的数量与比例及其相互关系,应用Western blot观察转移相关因子的表达。结果肿瘤转移灶及尚未形成转移的常见部位均可见VEGFR1阳性造血祖细胞细胞簇,并且与肿瘤转移的时间呈正相关,而无肿瘤裸鼠未见此细胞簇形成;在肿瘤转移过程中,基质金属蛋白酶9、基质细胞衍生因子1蛋白表达逐渐增强。结论VEGFR1阳性造血祖细胞簇形成总是伴随大肠癌转移,可能促进转移相关因子表达,促成转移的发生。

Objective To investigate the relation of vascular endothelial growth factor receptor 1（VEGFR1）-positive hematopoietic progenitor cell with the metastasis of human colorectal carcinoma. Methods Human colorectal cancer cells SW480/M5 were implanted into BALB/c nude mice, and the tumor tissue blocks were re-implantated into the colon of nude mice. The quantity and percentage of VEGFRl-positive hematopoietic progenitor cells and human colbrectal cancer cells in the pre-metastatic location were observed with flow cytometry, and the expression of metastasis-related factors was detected using Western blotting. Results Bone marrow-derived hematopoietic progenitor cells expressing VEGFRI were found in the common pre-metastatic sites and formed cell clusters before the arrival of the tumor cells, but these cells were not detected in nude mice without tumor implantation. In the course of tumor metastasis, the expression of the proteinases including matrix metalloproteinase 9 and stromal cell-derived factor 1 gradually intensified within the metastatic niche. Conclusion The formation of VEGFRl-positive hematopoietic progenitor cellular clusters is accompanied by the metastasis of human colorectal cancer, and may enhance the expression of metastasis-related factors, suggesting its important role in the invasion and metastasis of colorectal cancer.