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人骨髓间充质干细胞可营造免疫抑制微环境并促进小鼠乳腺癌发生。

Human mesenchymal stem cells creating an immunosuppressive environment and promote breast cancer in mice.

机构信息

Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.

出版信息

Sci Rep. 2013;3:2298. doi: 10.1038/srep02298.

Abstract

Human mesenchymal stem cells (hMSC) can home to tumor sites and promote tumor growth. The effects of hMSC on tumor growth are controversial and involvement of hMSC in tumor immunology has not been adequately addressed. Therefore, we investigated whether injection of hMSC affects tumor appearance, growth and metastasis, and anti-tumor immunity in an experimental animal model of metastatic breast cancer. Injection of hMSC in BALB/c mice bearing mammary carcinoma promoted tumor growth and metastasis, which was accompanied by lower cytotoxic activity of splenocytes, NK cells and CD8⁺ T cells in vitro. Tumor-bearing mice that received hMSC had significantly lower percentages of CD3⁺NKp46⁺ NKT-like, higher percentages of CD4⁺Foxp3⁺ T cells, increased serum levels of Th2 and decreased serum levels of Th1 cytokines, and significantly higher number of CD4⁺ cells expressing IL-10. These results demonstrate that immunosuppressive environment created by hMSC promoted breast tumor growth and metastasis in mice.

摘要

人骨髓间充质干细胞(hMSC)可以归巢至肿瘤部位并促进肿瘤生长。hMSC 对肿瘤生长的影响存在争议,其在肿瘤免疫学中的作用尚未得到充分解决。因此,我们研究了 hMSC 的注射是否会影响转移性乳腺癌实验动物模型中的肿瘤外观、生长和转移以及抗肿瘤免疫。在携带乳腺癌的 BALB/c 小鼠中注射 hMSC 可促进肿瘤生长和转移,这伴随着脾细胞、NK 细胞和 CD8⁺ T 细胞体外细胞毒性活性降低。接受 hMSC 的荷瘤小鼠的 CD3⁺NKp46⁺NKT 样细胞比例显著降低,CD4⁺Foxp3⁺T 细胞比例升高,血清 Th2 细胞因子水平升高,Th1 细胞因子水平降低,并且表达 IL-10 的 CD4⁺细胞数量显著增加。这些结果表明,hMSC 所创造的免疫抑制环境促进了小鼠的乳腺癌生长和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9445/3725512/6f8d283611aa/srep02298-f1.jpg

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