Background and objective: Mesenchymal stem cells (MSC) are adult stem cells derived from mesoderm. Evidence has shown that MSC could migrate towards tumor tissue and differentiate into tumor associated fibroblast in tumor microenvironment, which influences tumor growth and metastasis. However, the reports of MSC in non-small cell lung cancer (NSCLC) are few and controversial. The aim of this study is to explore the chemotaxis of MSC towards NSCLC and to test the effects of MSC on the proliferation and invasion ability of NSCLC.
Methods: Transwell assay was used to test MSC and NSCLC migration and invasion, and Thymidine incorporation assay was adopted to measure NSCLC cells proliferation. The expression of interleukin-6 (IL-6), insulinlike growth factor (IGF-1), vascular endothelial growth factor (VEGF) and dickkopf-related protein 1 (DKK1) of MSCs were determined by real time PCR. A549 lung cancer xenograft animal tumor model was set up to evaluate the MSC effect in vivo.
Results: Lung cancer cells could attract MSC tropism. MSC conditioned medium favored lung cancer cell proliferation and lung cancer cells stimulated the expression of IL-6, IGF-1, VEGF and DKK1 on MSCs. In vivo animal study showed that the tumor with MSC injection grew much faster compared to control group.
Conclusions: MSCs could migrate towards NSCLC cells and favor tumor growth. In turn, NSCLC cells could stimulate the overexpression of cytokines on MSCs which are essential for the tumor growth.
背景与目的 间充质干细胞（mesenchymal stem cells, MSC）是来源于中胚层的成体干细胞。有文献报道MSC通过向肿瘤组织的归巢和向间质成分分化，改变肿瘤微环境，影响肿瘤的生长和转移。但MSC在非小细胞肺癌（non-small cell lung cancer, NSCLC）中的作用报道较少，且不一致。本研究旨在探讨MSC向NSCLC细胞的趋化能力，以及其对NSCLC细胞的增殖和侵袭能力的作用。方法 Transwell法检测MSC向肺癌细胞迁移能力，Thymidine 嵌入实验检测MSC条件培养液对肺癌细胞增殖能力的影响，Real-time PCR法检测肺癌/MSC共培养后MSC表达白介素（interleukin-6, IL-6）、胰岛素样生长因子（insulinlike growth factor, IGF-1）、血管内皮生长因子（vascular endothelial growth factor, VEGF)和Dickkopf相关蛋白1（dickkopf-related protein 1, DKK1）的变化。建立人肺癌A549细胞裸鼠皮下荷瘤模型，给予MSC细胞，定期测量肿瘤体积变化。结果 MSC可以向肺癌细胞趋化运动，其条件培养液可以促进肺癌细胞的增殖能力。肺癌细胞反过来可以促进MSC过表达IL-6、IGF-1、VEGF和DKK1。体内试验显示MSC注射组的肿瘤体积明显大于对照组。结论 MSC可以向肺癌细胞趋化并促进肺癌的生长。反过来，肺癌细胞可以刺激MSC过表达生长因子进一步促进肿瘤生长。.