Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids

Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D spheroids
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ALP 和 MMP9 活性的诱导促进异质人类 BMSC 和 HNSCC 3D 球体中的侵袭行为

DOI:
10.1096/fj.201900925r
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发表时间:
2019
期刊:
The FASEB Journal
影响因子:
--
通讯作者:
Bauer RJ
Bauer RJ
中科院分区:
--
文献类型:
--
作者:
Wessely A;Waltera A;Reichert TE;Stöckl S;Grässel S;Bauer RJ

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间充质干细胞(MSC)是一种多能祖细胞,能够分化为脂肪细胞、成骨细胞、软骨细胞和肌细胞谱系。越来越多的证据表明,MSC被各种信号如趋化因子、生长因子和细胞因子吸引到肿瘤微环境中。肿瘤归巢干细胞可以来源于骨髓来源的MSC(BMSC)或脂肪组织来源的MSC。最近的科学数据表明,MSC与肿瘤细胞结合可以促进或抑制肿瘤发生行为。在头颈部鳞状细胞癌(HNSCC)中,据报道BMSC富集有潜在的负面作用。在这里,我们评估了来自4个不同供体的BMSC与4个HNSCC细胞系在三维多细胞球体模型中的作用。异质性组合显示成骨标志物侏儒相关转录因子2(RUNX 2)和碱性磷酸酶(ALP)的基因和蛋白表达上调,以及基质金属蛋白酶9的大量分泌。此外,异源BMSC/肿瘤球状体在Boyden室侵袭测定中显示出与同质球状体相比增加的侵袭。此外,ALP的抑制导致在一个显着减少的蔓延的异质球体层粘连蛋白丰富的基质。总之,我们的数据表明BMSC与HNSCC组合的促转移作用。Wessely,A.,Waltera,A.,Reichert,T. E、Stöckl,S.,Grässel,S.,鲍尔河,巴西-地J. ALP和MMP 9活性的诱导促进异质性人BMSC和HNSCC 3D-球状体中的侵袭行为。
Mesenchymal stem cells (MSCs) are multipotent progenitor cells capable of differentiating into adipocytic, osteogenic, chondrogenic, and myogenic lineages. There is growing evidence that MSCs home into the tumor microenvironment attracted by a variety of signals such as chemokines, growth factors, and cytokines. Tumor-homing stem cells may originate from bone marrow–derived MSCs (BMSCs) or adipose tissue-derived MSCs. Recent scientific data suggest that MSCs in combination with tumor cells can either promote or inhibit tumorigenic behavior. In head and neck squamous cell carcinoma (HNSCC), BMSCs are reported to be enriched with a potential negative role. Here, we evaluated the effect of BMSCs from 4 different donors in combination with 4 HNSCC cell lines in a 3-dimensional multicellular spheroid model. Heterogeneous combinations revealed an up-regulation of gene and protein expression of osteogenic markers runt-related transcription factor 2 (RUNX2) and alkaline phosphatase (ALP) together with a substantial secretion of matrix metalloproteinase 9. Moreover, heterogenous BMSC/tumor spheroids showed increased invasion compared with homogenous spheroids in a Boyden chamber invasion assay. Furthermore, inhibition of ALP resulted in a substantially decreased spreading of heterogeneous spheroids on laminin-rich matrix. In summary, our data suggest a prometastatic effect of BMSCs combined with HNSCC.—Wessely, A., Waltera, A., Reichert, T. E., Stöckl, S., Grässel, S., Bauer, R. J. Induction of ALP and MMP9 activity facilitates invasive behavior in heterogeneous human BMSC and HNSCC 3D-spheroids.
DOI: 10.1089/scd.2010.0139
发表时间: 2011-01-01
影响因子: 4
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通讯作者: Houghton, JeanMarie
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