Huang Bo, Feng Zhichun, Zhu Lina, Zhang Sheng, Duan Jun, Zhao Chaochao, Zhang Xiaoying
Public Health, Guilin Medical University, Guilin 541100, People's Republic of China.
Affiliated BaYi Children's Hospital, Seventh Medical Center of PLA General Hospital, Beijing 100700, People's Republic of China.
Onco Targets Ther. 2021 Jan 6;14:67-81. doi: 10.2147/OTT.S282322. eCollection 2021.
Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, there has been gained further interest in the relationship between MSCs and tumorigenesis. MSCs are reported to both promote and abrogate tumor growth. The present study was designed to investigate whether miRNAs are involved in the interactions between MSCs and tumor cells in the tumor microenvironment.
Rat bone marrow-derived MSCs (rMSCs) were cultured with or without tumor-conditioned medium (TCM) to observe the effect upon MSCs by TCM. Microarrays and real-time PCR were performed between the two groups. A series of experiments were used to reveal the functional significance of microRNA-503 (miR-503) in rMSCs. Furthermore, the antitumorigenic effect of silencing of miR-503 in rMSCs (miR-503-i-rMSCs) in vivo was measured.
We found that rMSCs in vitro exhibited tumor-promoting properties in TCM, and the microRNA profiles of rMSCs were significantly altered in TCM. However, miR-503-i-rMSCs can decrease the angiogenesis and growth of A549 cells. We also demonstrated in an in vivo tumor model that miR-503-i-rMSCs inhibited A549 tumor angiogenesis and significantly abrogated tumor initiation and growth. CD133 assays in peripheral blood and A549 xenografts further validated that miR-503-i-rMSCs, rather than rMSCs, exerted an antitumorigenic action in the A549 tumor model.
Our results suggest that miR-503-i-rMSCs are capable of tumor suppression. Further studies are required to develop clinical therapies based on the inhibition of the tumor-promoting properties and potentiation of the anti-tumor properties of MSCs.
间充质干细胞（MSCs）因其潜在的临床应用价值而受到广泛研究。近来，人们对MSCs与肿瘤发生之间的关系产生了更大的兴趣。据报道，MSCs既能促进肿瘤生长，也能抑制肿瘤生长。本研究旨在探讨微小RNA（miRNAs）是否参与肿瘤微环境中MSCs与肿瘤细胞之间的相互作用。
将大鼠骨髓来源的MSCs（rMSCs）与肿瘤条件培养基（TCM）一起培养或不与TCM一起培养，以观察TCM对MSCs的影响。对两组进行微阵列和实时聚合酶链反应。采用一系列实验揭示微小RNA-503（miR-503）在rMSCs中的功能意义。此外，还检测了体内rMSCs中miR-503沉默（miR-503-i-rMSCs）的抗肿瘤作用。
我们发现体外培养的rMSCs在TCM中表现出促肿瘤特性，且rMSCs的微小RNA谱在TCM中发生了显著改变。然而，miR-503-i-rMSCs可降低A549细胞的血管生成和生长。我们还在体内肿瘤模型中证明，miR-503-i-rMSCs抑制A549肿瘤血管生成，并显著抑制肿瘤起始和生长。外周血和A549异种移植瘤中的CD133检测进一步证实，在A549肿瘤模型中，miR-503-i-rMSCs而非rMSCs发挥了抗肿瘤作用。
我们的结果表明，miR-503-i-rMSCs具有肿瘤抑制能力。需要进一步研究以开发基于抑制MSCs促肿瘤特性和增强其抗肿瘤特性的临床治疗方法。
