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造血祖细胞对结肠癌肿瘤干细胞生物学特性的影响。

Effect of hematopoietic progenitor cells on the biological characteristics of colon cancer tumor stem cells.

作者信息

Guan Shen, Yang Chunkang, Wu Lihuo

机构信息

Department of Gastrointestinal Surgical Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China.

General Surgery Department, Fuqing City Hospital, Fuzhou, China.

出版信息

Transl Cancer Res. 2021 Feb;10(2):714-723. doi: 10.21037/tcr-20-2810.

Abstract

BACKGROUND

Cancer stem cells (CSCs) are a type of tumor cell that are self-sustaining and can differentiate into several different types of cells. The present study aims to investigate the effect of hematopoietic progenitor cells (HPCs) on the biological behavior of colon CSCs (CCSCs) and to determine the underlying molecular mechanisms of liver metastasis in colorectal cancer.

METHODS

Subsets of CCSCs were isolated from stem-like HCT116 cells and cocultured with CD133 HPCs in vitro. Colony formation assay, and CCK-8 were used to assess the effects of HPCs on CCSC subsets. Invasive and migration assay were done to study the effects of HPCs mediated metastatic capacity of CCSC subsets. Expression of MMP-9, VEGF, E-cadherin and β-catenin was analyzed by qPCR and Western blotting.

RESULTS

CCK-8 and colony formation assays showed that HPCs significantly promoted proliferation and colony formation of the CCSC subsets (P=0.031). HPCs also significantly enhanced the migration (P=0.011) and invasive capacity (P=0.001) of the CCSC subsets. Quantitative PCR showed that MMP-9 and VEGF expression in CCSC subsets were significantly upregulated (P=0.000 and P=0.005). Western blotting showed that MMP-9, VEGF and β-catenin expression in CCSC subsets were significantly upregulated (P=0.000, P=0.005, P=0.000). The protein expression levels of E-cadherin in the CCSC subsets was significantly downregulated (P=0.002).

CONCLUSIONS

CD133 HPCs enhanced migration, invasion and proliferation of CCSC subsets .

摘要

背景

癌症干细胞(CSCs)是一类能够自我维持并可分化为几种不同类型细胞的肿瘤细胞。本研究旨在探讨造血祖细胞(HPCs)对结肠癌症干细胞(CCSCs)生物学行为的影响,并确定结直肠癌肝转移的潜在分子机制。

方法

从干细胞样HCT116细胞中分离出CCSCs亚群,并在体外与CD133 HPCs共培养。采用集落形成试验和CCK-8法评估HPCs对CCSCs亚群的影响。进行侵袭和迁移试验以研究HPCs介导的CCSCs亚群转移能力的影响。通过qPCR和蛋白质印迹法分析MMP-9、VEGF、E-钙黏蛋白和β-连环蛋白的表达。

结果

CCK-8和集落形成试验表明,HPCs显著促进了CCSCs亚群的增殖和集落形成(P = 0.031)。HPCs还显著增强了CCSCs亚群的迁移能力(P = 0.011)和侵袭能力(P = 0.001)。定量PCR显示,CCSCs亚群中MMP-9和VEGF的表达显著上调(P = 0.000和P = 0.005)。蛋白质印迹法显示,CCSCs亚群中MMP-9、VEGF和β-连环蛋白的表达显著上调(P = 0.000、P = 0.005、P = 0.000)。CCSCs亚群中E-钙黏蛋白的蛋白质表达水平显著下调(P = 0.002)。

结论

CD133 HPCs增强了CCSCs亚群的迁移、侵袭和增殖能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b51/8797965/eb80ce79f9a1/tcr-10-02-714-f1.jpg

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