Human CD133-positive hematopoietic progenitor cells initiate growth and metastasis of colorectal cancer cells
Human CD133-positive hematopoietic progenitor cells initiate growth and metastasis of colorectal cancer cells
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人类CD133阳性造血祖细胞启动结直肠癌细胞的生长和转移
DOI：
10.1093/carcin/bgu192
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发表时间：
2014-12-01
期刊：
影响因子：
4.7
通讯作者：
Li, Xue-Nong
中科院分区：
文献类型：
--
作者：
Zhang, Chao;Zhou, Chang;Li, Xue-Nong
肿瘤特异性的“转移前生态位”已成为肿瘤转移的潜在驱动力，并已通过小鼠癌症转移模型得到证实。血管内皮生长因子受体-1（+）造血祖细胞（HPCs）已被证明在转移中发挥重要作用，在远处肿瘤进展的指定部位形成“转移前生态位”。在这里，CD133+人脐带血造血祖细胞（HUHPCs）从人脐带血中纯化并在体外扩增。我们通过细胞间共培养研究了CD133+ HUHPCs对四种结直肠癌（CRC）细胞系生长和转移的影响。我们的研究结果表明，CD133+ HUHPCs在体外促进CRC细胞的增殖和侵袭，在体内促进肿瘤的生长和转移。此外，联合注射SW480/EGFP+细胞和HUHPCs后，通过免疫组化分析，在转移前肝组织中观察到CD133+ HUHPCs。因此，我们进行了进一步的实验，以揭示CD133+ HUHPCs影响结肠癌发生和癌症进展的分子机制。利用凝胶电泳技术对提取的蛋白质进行二维差分分离。在这些差异表达的蛋白中，丝裂原活化蛋白4激酶4、基质细胞衍生因子-1、基质金属肽酶9、钙蛋白、外周蛋白、亮氨酸拉链蛋白、推定肿瘤抑制因子1和鸟嘌呤醋酸酯甲基转移酶引起了我们的注意。Western blot分析进一步证实了这些蛋白的差异表达。总之，这些结果表明CD133+ HUHPCs可能通过提供转移前微环境诱导CRC细胞增殖或转移，并影响其衍生蛋白。
The tumour-specific 'pre-metastatic niche' has emerged as a potential driving force for tumour metastasis and has been confirmed using mouse models of cancer metastasis. Vascular endothelial growth factor receptor-1(+) hematopoietic progenitor cells (HPCs) have been shown to play an important role in metastasis, forming a 'pre-metastatic niche' at designated sites for distant tumour progression. Here, CD133+ human umbilical hematopoietic progenitor cells (HUHPCs) were purified from human umbilical cord blood and expanded in vitro. We studied the effects of CD133+ HUHPCs on the growth and metastasis of four colorectal cancer (CRC) cell lines by using cell-to-cell co-culture. Our results revealed that CD133+ HUHPCs promoted the proliferation and invasion of CRC cells in vitro and enhanced tumour growth and metastasis in vivo. Moreover, CD133+ HUHPCs were observed in the pre-metastatic liver tissue using immunohistochemical analysis after co-injection of SW480/EGFP+ cells and HUHPCs. Further experiments were therefore conducted to uncover the molecular mechanisms by which CD133+ HUHPCs influenced colon carcinogenesis and cancer progression. Extracted proteins were separated using the two-dimensional difference in gel electrophoresis technology. Among the differentially expressed proteins, mitogen-activated protein 4 kinase 4, stromal cell-derived factor-1, matrix metallopeptidase 9, calumenin, peripherin, leucine zipper, putative tumour suppressor 1 and guanidinoacetate methyltransferase attracted our attention. Western blot analysis further confirmed the differential expression of these proteins. Altogether, these results suggest that CD133+ HUHPCs may induce proliferation or metastasis of CRC cells and impact their derived proteins by providing a pre-metastatic microenvironment.