Liu Tonggang, Zhu Kai, Ke Changkang, Yang Sanhu, Yang Feng, Li Zongfang, Zhang Zhipei
Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical UniversityXi'an, China.
The Center of Pulmonary Disease, Baoji Hi-tech People's HospitalBaoji, China.
Am J Transl Res. 2017 Jun 15;9(6):2891-2900. eCollection 2017.
Mesenchymal stem cells (MSCs) may play a significant role in carcinogenesis; however, data have shown that MSCs can both promote and inhibit tumor growth. We investigated the effect of MSCs on the development of lung cancer in a rat model. Bone marrow-derived MSCs were isolated from male Wistar rats and fluorescently labeled. Genotoxic carcinogens 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN) were instilled into the left lung lobes of female rats to induce tumors. Labeled male MSCs were infused into the female rats via tail vein, and the rats were sacrificed on days 3 and 7. MSC survival and distribution were detected by PCR and fluorescence, respectively. Labeled MSCs aggregated at the injection site in the left lobe (MCA/DEN-treated) on day 3 but not the untreated right lobe. Survival of the MSCs in vivo was confirmed by detection of the male SRY gene in lung tissues by PCR at day 3; however, by day 7, lung tissues were SRY-negative. Next, carcinogen-treated rats were divided into two groups and infused with normal MSCs (experimental group) or PBS (control group) every week for 10 weeks, then sacrificed. Cell proliferation in lung tissues was calculated by Ki67 and PCNA expression. Eighty-percent (8/10) of rats in the control group had tumors, while none of the rats in the experimental group had tumors. There was no difference in cell proliferation in lung tissues between the groups. Therefore, bone marrow-derived MSCs prevented development of carcinogen-induced lung cancer in a rat model. Additional studies are needed to determine mechanism.
间充质干细胞（MSCs）可能在致癌过程中发挥重要作用；然而，数据表明MSCs既能促进肿瘤生长，也能抑制肿瘤生长。我们在大鼠模型中研究了MSCs对肺癌发生发展的影响。从雄性Wistar大鼠中分离出骨髓来源的MSCs并进行荧光标记。将遗传毒性致癌物3-甲基胆蒽（MCA）和二乙基亚硝胺（DEN）注入雌性大鼠的左肺叶以诱导肿瘤。将标记的雄性MSCs通过尾静脉注入雌性大鼠体内，并在第3天和第7天处死大鼠。分别通过PCR和荧光检测MSCs的存活和分布情况。在第3天，标记的MSCs聚集在左叶（MCA/DEN处理组）的注射部位，而未处理的右叶则没有。通过在第3天通过PCR检测肺组织中的雄性SRY基因证实了MSCs在体内的存活；然而，到第7天，肺组织SRY呈阴性。接下来，将致癌物处理的大鼠分为两组，每周注入正常MSCs（实验组）或PBS（对照组），持续10周，然后处死。通过Ki67和PCNA表达计算肺组织中的细胞增殖情况。对照组80%（8/10）的大鼠患有肿瘤，而实验组的大鼠均未患肿瘤。两组肺组织中的细胞增殖没有差异。因此，骨髓来源的MSCs在大鼠模型中阻止了致癌物诱导的肺癌的发生发展。需要进一步研究以确定其机制。
