Cell Cycle 2011 Sep;10 (18): 3198-207. [IF:4.999]
Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor growth.
Zhu W , Huang L , Li Y , Qian H , Shan X , Yan Y , Mao F , Wu X , Xu WR .
School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.
江苏大学医学院，医学实验室
Abstract
In previous studies, we and others have shown that bone marrow mesenchymal stem cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in mouse xenograft models, suggesting that interactions between MSCs and tumor cells may play an important role in this process. However, the exact mechanism remains unclear. In the present study, we investigated whether the physical presence or the continuous presence of MSCs is required for enhanced tumor growth, and we found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC-conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth comparable to the effect of MSC co-injection in vivo in mouse xenograft models. We further showed that significant tumor modifying activity is present in post-ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM induces the expression of VEGF of tumor cells as well as the activation of RhoA-GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in serial transplantation, suggesting that MSC-secreted factors have profound effects on "reprogramming" of tumor growth. Our data provide new insights into the way in which MSCs modify tumor growth and offer a new and exciting opportunity to develop effective therapeutics for intercepting tumor progression.
摘要
在已往的研究中，我们和其他研究者表明：骨髓间质干细胞（MSCs）能够修复肿瘤生长的部位和促进小鼠异体移植模型中的肿瘤生长，这表明干细胞和肿瘤细胞之间的某种关系在这一过程中发挥了重要作用。然而，确切的机制尚未明确。在本项研究中，我们观察这种关系是否存在，MSCs是否促进肿瘤生长。我们发现与在异种移植模型小鼠体内注射MSC的效果相比，在体外单剂量的人类条件培养液（HMSC- CM）对肿瘤细胞SGC- 7901进行预处理是足够促进肿瘤生长的。我们进一步研究表明，显著的肿瘤修改活动现象存在于可溶性信号分子。生化分析表明，HMSC- CM诱导肿瘤细胞以及血管内皮生长因子的表达，激活RhoA-GTPase 和 ERK1/2.。此外，HMSC CM能够在移植后可持续的增强肿瘤生长，这表明MSC分泌的因子对肿瘤生长的“重新编程”的重大作用。我们的数据为MSCs的修改肿瘤的生长提供了新的见解，为制定有效拦截肿瘤进展提供了新的有效方法。
