伤口液对人骨髓间充质干细胞向癌症相关成纤维细胞转分化的影响

IF 2.9 4区 生物学 Q1 ANATOMY & MORPHOLOGY
Helena Moratin, Sonja Böhm, Rudolf Hagen, Agmal Scherzad, Stephan Hackenberg
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引用次数: 0

摘要

肿瘤微环境中的癌相关成纤维细胞(CAF)对肿瘤生长和转移行为具有决定性影响。细胞起源以及导致CAF形成的刺激是异质的,阻碍了精确的表征。本研究旨在通过RT-PCR分析创面愈合过程中分泌的细胞因子、肿瘤细胞相关的旁分泌因子以及细胞间直接接触对间充质干细胞(MSC)中纤维母细胞激活蛋白(FAP)、α-平滑肌肌动蛋白(α-SMA)、血栓响应蛋白-1 (THBS1)、腱蛋白-c (TNC)表达的影响。细胞与创面液(WF)孵育后出现不同的形态特征。此外,与肿瘤条件培养基和与肿瘤细胞共培养相比,WF后MSC中FAP和α-SMA的表达显著降低;不同孵育方法对THBS1和TNC均无显著影响。免疫组化分析未见FAP和α-SMA表达模式的改变。点印迹法发现培养基中细胞因子组成存在差异。结果的异质性强调了肿瘤细胞和微环境细胞相互作用的复杂性,特别是通过添加人源性WF。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Influence of Wound Fluid on the Transdifferentiation of Human Mesenchymal Bone Marrow Stem Cells into Cancer-Associated Fibroblasts.

Cancer-associated fibroblasts (CAF) in the tumor microenvironment have a decisive influence on tumor growth and metastatic behavior. The cellular origins as well as the stimuli leading to CAF formation are heterogenous, impeding a precise characterization. Aim of this study was to analyze the influence of cytokines secreted in the process of wound healing, tumor cell-associated paracrine-secreted factors, and direct cell-cell contact on the expression of the CAF-associated markers fibroblast activation protein (FAP), α-smooth muscle actin (α-SMA), thrombospondin-1 (THBS1), and tenascin-c (TNC) by RT-PCR in mesenchymal stem cells (MSC). Cells developed different morphological characteristics after incubation with wound fluid (WF). Moreover, expression of FAP and α-SMA in MSC was significantly reduced after WF compared to tumor-conditioned medium and in co-culture with tumor cells; THBS1 and TNC were not significantly altered after any of the different incubation methods. There were no alterations of expression patterns of FAP and α-SMA in the immunohistochemical analysis. Differ-ences in the cytokine composition of the media were found in the dot blot. The heterogeneity of the results emphasizes the complexity of the interactions of tumor cells and cells of the microenvironment, particularly through the addition of human-derived WF.

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来源期刊
Cells Tissues Organs
Cells Tissues Organs 生物-发育生物学
CiteScore
4.90
自引率
3.70%
发文量
45
审稿时长
6-12 weeks
期刊介绍: ''Cells Tissues Organs'' aims at bridging the gap between cell biology and developmental biology and the emerging fields of regenerative medicine (stem cell biology, tissue engineering, artificial organs, in vitro systems and transplantation biology). CTO offers a rapid and fair peer-review and exquisite reproduction quality. Special topic issues, entire issues of the journal devoted to a single research topic within the range of interests of the journal, are published at irregular intervals.
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