Abstract

Background

Mesenchymal stemlike cells (MSLCs) have been detected in many types of cancer including brain tumors and have received attention as stromal cells in the tumor microenvironment. However, the cellular mechanisms underlying their participation in cancer progression remain largely unexplored. The aim of this study was to determine whether MSLCs have a tumorigenic role in brain tumors.

Methods

To figure out molecular and cellular mechanisms in glioma invasion, we have cultured glioma with MSLCs in a co-culture system.

Results

Here, we show that MSLCs in human glioblastoma (GBM) secrete complement component C5a, which is known for its role as a complement factor. MSLC-secreted C5a increases expression of zinc finger E-box-binding homeobox 1 (ZEB1) via activation of p38 mitogen-activated protein kinase (MAPK) in GBM cells, thereby enhancing the invasion of GBM cells into parenchymal brain tissue.

Conclusion

Our results reveal a mechanism by which MSLCs undergo crosstalk with GBM cells through the C5a/p38 MAPK/ZEB1 signaling loop and act as a booster in GBM progression.

Key Points

1. MSLCs activate p38 MAPK-ZEB1 signaling in GBM cells through C5a in a paracrine manner, thereby boosting the invasiveness of GBM cells in the tumor microenvironment.2. Neutralizing of C5a could be a potential therapeutic target for GBM by inhibition of mesenchymal phenotype.

中文翻译：

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GBM细胞与间充质干细胞之间的串扰通过C5a/p38/ZEB1轴促进GBM的侵袭性

摘要

背景

间充质干细胞（MSLC）已在包括脑肿瘤在内的多种癌症中检测到，并作为肿瘤微环境中的基质细胞受到关注。然而，它们参与癌症进展的细胞机制在很大程度上仍未被探索。本研究的目的是确定 MSLC 是否在脑肿瘤中具有致瘤作用。

方法

为了弄清楚胶质瘤侵袭的分子和细胞机制，我们在共培养系统中培养了胶质瘤和 MSLC。

结果

在这里，我们显示人胶质母细胞瘤 (GBM) 中的 MSLC 分泌补体成分 C5a，C5a 以其作为补体因子的作用而闻名。MSLC 分泌的 C5a 通过激活 GBM 细胞中的 p38 丝裂原活化蛋白激酶 (MAPK) 增加锌指 E-box 结合同源框 1 (ZEB1) 的表达，从而增强 GBM 细胞对脑实质组织的侵袭。

结论

我们的研究结果揭示了一种机制，MSLC 通过 C5a/p38 MAPK/ZEB1 信号环路与 GBM 细胞发生串扰，并作为 GBM 进展的助推器。

关键点

1. MSLCs通过C5a旁分泌方式激活GBM细胞中p38 MAPK-ZEB1信号通路，从而增强GBM细胞在肿瘤微环境中的侵袭能力。 2．通过抑制间充质表型，中和 C5a 可能成为 GBM 的潜在治疗靶点。