Department of Thoracic Surgery, Qilu Hospital, Shandong University, Jinan, PR China.
J Cell Physiol. 2011 Jul;226(7):1860-7. doi: 10.1002/jcp.22511.
Nowadays, some evidences demonstrate that human mesenchymal stem cells (hMSCs) favor tumor growth; however, others show that hMSCs can suppress tumorigenesis and tumor growth. With the indeterminateness of the effect of hMSCs on tumors, we investigated the effect of hMSCs on lung cancer cell line A549 and esophageal cancer cell line Eca-109 in vitro and in vivo. Our results revealed that hMSCs inhibited the proliferation and invasion of A549 and Eca-109 cells, arrested tumor cells in the G1 phase of the cell cycle and induced the apoptosis of tumor cells in vitro by using a co-culture system and the hMSCs-conditioned medium. However, animal study showed that hMSCs enhanced tumor formation and growth in vivo. Western blotting and immunoprecipitation data showed that the expressions of proliferating cell nuclear antigen (PCNA), Cyclin E, phospho-retinoblastoma protein (pRb), B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL, and matrix metalloproteinase 2 (MMP-2) were downregulated and the formation of Cyclin E-cyclin-dependent kinase 2 (CDK2) complexes was inhibited in the tumor cells treated with the hMSCs-conditioned medium. According to the observation of tumor mass and the result of microvessel density (MVD), we found that the promoting role of hMSCs on tumor growth was related with the increase of tumor vessel formation. Our present study suggests that hMSCs have a contradictory effect on tumor cell growth between in vitro and in vivo, and therefore, the exploitation of hMSCs in new therapeutic strategies should be cautious under the malignant conditions.
如今,有一些证据表明人类间充质干细胞(hMSCs)有利于肿瘤生长;然而,也有其他证据表明 hMSCs 可以抑制肿瘤发生和肿瘤生长。鉴于 hMSCs 对肿瘤影响的不确定性,我们研究了 hMSCs 在体外和体内对肺癌细胞系 A549 和食管癌细胞系 Eca-109 的作用。我们的结果表明,hMSCs 通过共培养系统和 hMSCs 条件培养基抑制 A549 和 Eca-109 细胞的增殖和侵袭,将肿瘤细胞阻滞在细胞周期的 G1 期,并诱导肿瘤细胞凋亡。然而,动物研究表明,hMSCs 增强了体内肿瘤的形成和生长。Western blot 和免疫沉淀数据显示,增殖细胞核抗原(PCNA)、细胞周期蛋白 E、磷酸化视网膜母细胞瘤蛋白(pRb)、B 细胞淋巴瘤/白血病-2(Bcl-2)、Bcl-xL 和基质金属蛋白酶 2(MMP-2)的表达下调,并且用 hMSCs 条件培养基处理的肿瘤细胞中细胞周期蛋白 E-细胞周期蛋白依赖性激酶 2(CDK2)复合物的形成受到抑制。根据肿瘤质量的观察和微血管密度(MVD)的结果,我们发现 hMSCs 对肿瘤生长的促进作用与肿瘤血管形成的增加有关。本研究表明,hMSCs 在体外和体内对肿瘤细胞生长的作用具有矛盾性,因此,在恶性条件下,应谨慎利用 hMSCs 开发新的治疗策略。