Mesenchymal stem cells utilize CXCR4-SDF-1 signaling for acute, but not chronic, trafficking to gastric mucosal inflammation.
Mesenchymal stem cells utilize CXCR4-SDF-1 signaling for acute, but not chronic, trafficking to gastric mucosal inflammation.
复制标题
间充质干细胞利用CXCR4-SDF-1信号传导急性，但没有慢性运输到胃粘膜炎症。
DOI：
10.1007/s10620-013-2782-y
复制
发表时间：
2013-09
影响因子：
3.1
通讯作者：
Houghton, JeanMarie
中科院分区：
文献类型：
--
作者：
Stoicov, Calin;Li, Hanchen;Liu, Jian Hua;Houghton, JeanMarie
幽门螺杆菌感染是胃癌发生的主要危险因素。间充质干细胞（MSCs）是非造血基质细胞，能够分化成不同的细胞系。间充质干细胞通过直接形成肿瘤、促进微环境或促进血管生成和转移来促进癌症的发展。CXCR4/SDF-1轴被MSC用于在慢性炎症部位的运输、归巢和植入，并在肿瘤发生中发挥重要作用。确定CXCR4受体是否在MSC对幽门螺杆菌介导的胃癌的发展中起作用。采用RT-PCR方法检测急性和慢性炎症小鼠胃黏膜中SDF-1和CXCR4的表达。小鼠培养适应的MSC表达CXCR4。将感染幽门螺杆菌6个月的野生型C57BL/6小鼠或对照组静脉注射CXCR4敲除的MSC。对动物进行了另外4个月的随访。采用RT-PCR方法定量测定MSC在胃中的归巢情况。采用免疫组织化学和荧光原位杂交技术分析间充质干细胞向胃上皮细胞系的分化。CXCR4和SDF-1在幽门螺杆菌诱导的慢性胃炎症中均上调。在急性胃炎症中，间充质干细胞归巢到胃中完全需要CXCR4，但在幽门螺杆菌诱导的胃癌中仅部分需要CXCR4。MSC早在幽门螺杆菌感染10个月时就可导致胃上皮内瘤变。我们的研究结果表明，MSC通过促进小鼠胃癌的加速形式具有致瘤作用。MSC在慢性炎症中的植入仅部分依赖于cxcr4。
Helicobacter infection is the main risk factor in developing gastric cancer. Mesenchymal stem cells (MSCs) are non-hematopoietic stromal cells, which are able to differentiate into different cell lineages. MSC contribute to cancer development by forming the tumor directly, contributing to the microenvironment, or by promoting angiogenesis and metastasis. CXCR4/SDF-1 axis is used by MSC in trafficking, homing, and engraftment at chronic inflammation sites, and plays an important role in tumorigenesis. To determine if CXCR4 receptor has a role in MSC contribution to the development of Helicobacter-mediated gastric cancer. SDF-1 and CXCR4 expression in mouse gastric mucosa in the setting of acute and chronic inflammation was measured using RT-PCR. Mouse culture-adapted MSC express CXCR4. Wild-type C57BL/6 mice infected with Helicobacter felis for 6 months or controls were given IV injections of CXCR4 knock-down MSC. Animals were followed for another 4 months. Homing of MSC in the stomach was quantified using RT-PCR. MSC differentiation into gastric epithelia lineages was analyzed using immunohistochemistry and fluorescent in situ hybridization. CXCR4 and SDF-1 are both upregulated in the settings of Helicobacter-induced chronic gastric inflammation. CXCR4 is fully required for homing of MSC to the stomach in acute gastric inflammation, but only partially in Helicobacter-induced gastric cancer. MSC lead to gastric intraepithelial neoplasia as early as 10 months of Helicobacter infection. Our results show that MSC have a tumorigenic effect by promoting an accelerated form of gastric cancer in mice. The engraftment of MSC in chronic inflammation is only partially CXCR4-dependent.
登录
查看更多内容
影响因子：
4.6
作者：
Andrade, M. C.;Menezes, J. S.;Faria, A. M. C.
通讯作者：
Faria, A. M. C.
影响因子：
4.4
作者：
Ohmae, T;Hirata, Y;Omata, M
通讯作者：
Omata, M
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
11.2
作者：
Li, Hanchen;Fan, Xueli;Houghton, JeanMarie
通讯作者：
Houghton, JeanMarie
影响因子：
--
作者：
Kwak, MK;Hur, K;Yang, HK
通讯作者：
Yang, HK