Increased migration of human mesenchymal stromal cells by autocrine motility factor (AMF) resulted in enhanced recruitment towards hepatocellular carcinoma.
Increased migration of human mesenchymal stromal cells by autocrine motility factor (AMF) resulted in enhanced recruitment towards hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0095171
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mazzolini G
中科院分区：
文献类型：
--
作者：
Bayo J;Fiore E;Aquino JB;Malvicini M;Rizzo M;Peixoto E;Andriani O;Alaniz L;Piccioni F;Bolontrade M;Podhajcer O;Garcia MG;Mazzolini G
一些报道描述了人间充质基质细胞(MSCs)向肿瘤释放因子的迁移。自分泌运动因子(AMF)由包括肝细胞癌在内的多种肿瘤产生。本研究的目的是分析AMF在MSC向人肝细胞癌迁移中的作用。用Western分析评价肝癌细胞产生AMF的能力。用体外迁移实验分析AMF对不同来源(骨髓、脂肪组织和脐带血管周围细胞)间充质干细胞的影响，用酶谱和qRT-PCR分别检测MMP2的活性和关键基因的表达。为了评估AMF对体内MSC迁移的影响，进行了非侵入性荧光成像。为了检测AMF诱导的MSCs对肿瘤生长的影响，对其在体外的增殖、球体生长和体内肿瘤体积进行了评估。肝细胞癌产生的AMF在体外可诱导不同MSCs的迁移，并增强其MMP2活性。经重组AMF(RAMF)刺激后，MSCs与内皮细胞的黏附作用与MMP3、AMF受体、小窝蛋白-1、GDI-2的表达水平变化一致。重要的是，rAMF对MSCs的刺激增加了MSCs向实验性肝癌肿瘤的体内迁移。无论是在体内还是在体外，AMF诱导的MSCs对肝癌细胞都没有诱导促肿瘤作用。AMF在MSC向肝细胞癌的募集中发挥作用。然而，为了治疗的目的，它增加MSC向肝癌迁移的能力值得进一步评估。
Several reports described the migration of human mesenchymal stromal cells (MSCs) towards tumor-released factors. Autocrine motility factor (AMF) is produced by several tumors including hepatocellular carcinoma (HCC). The aim of this study was to analyze AMF involvement on MSC migration towards human HCC. Production of AMF by HCC tumors was evaluated by western analysis. The effects of AMF on MSCs from different sources (bone marrow, adipose tissue and perivascular cells from umbilical cord) were analyzed using in vitro migration assay; metalloproteinase 2 (MMP2) activity and expression of critical genes were studied by zymography and qRT-PCR, respectively. To assess AMF involvement on the in vivo MSC migration, noninvasive fluorescence imaging was performed. To test the effect of AMF-primed MSCs on tumor development, in vitro proliferation and spheroids growth and in vivo tumor volume were evaluated. AMF produced by HCC was found to induce migration of different MSCs in vitro and to enhance their MMP2 activity. Stimulation of MSCs with recombinant AMF (rAMF) also induced the in vitro adhesion to endothelial cells in coincidence with changes in the expression levels of MMP3, AMF receptor, caveolin-1, and -2 and GDI-2. Importantly, stimulation of MSCs with rAMF increased the in vivo migration of MSCs towards experimental HCC tumors. AMF-priming of MSCs did not induce a pro-tumorigenic effect on HCC cells neither in vivo nor in vitro. AMF plays a role in MSC recruitment towards HCC. However, its ability to increase MSC migration to HCC for therapeutic purposes merits further evaluation.
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影响因子：
10.1
作者：
De Becker, Ann;Van Hummelen, Paul;Van Riet, Ivan
通讯作者：
Van Riet, Ivan
影响因子：
5.2
作者：
Lopez Ponte, Adriana;Marais, Emeline;Domenech, Jorge
通讯作者：
Domenech, Jorge
DOI：
10.1073/pnas.83.10.3302
发表时间：
1986-05-01
影响因子：
11.1
作者：
LIOTTA, LA;MANDLER, R;SCHIFFMANN, E
通讯作者：
SCHIFFMANN, E
DOI：
10.1016/j.biocel.2008.07.011
发表时间：
2009-03-01
影响因子：
4
作者：
Kalwitz, Gregor;Endres, Michaela;Kaps, Christian
通讯作者：
Kaps, Christian
影响因子：
7.3
作者：
Dobashi, Y.;Watanabe, H.;Ooi, A.
通讯作者：
Ooi, A.