Department of Pathology and Laboratory Medicine, Brown University, Box G-8235, Providence, RI 02912, USA.
Anticancer Res. 2010 Jun;30(6):2153-60.
BACKGROUND/AIM: Tumor progression is influenced by the microenvironment. We found stem cells are recruited to malignant mesothelioma spheroids. We aimed to determine if stem cell recruitment depends on the chemokine SDF1, and if inhibition of the cognate receptor CXCR4 affects tumor growth.
The kinetics of stem cell recruitment was determined using immunofluorescence staining, BrdU incorporation and eGFP transgenic mice. Chemokines were identified using PCR array. Inhibitors of CXCR4 were used to determine the effect on cell migration and tumor progression.
The increasing number of stem cells found in tumor spheroids over time is attributed to cell recruitment. Stem cell migration in vitro was enhanced by exogenous SDF1 and abrogated by CXCR4 inhibition and. CXCR4 inhibition reduced tumor burden in vivo.
SDF1 is a candidate chemokine for recruitment of stem cells to malignant peritoneal mesothelioma and a potential target for therapy.
背景/目的:肿瘤的进展受微环境影响。我们发现干细胞被招募到恶性间皮瘤球体中。我们旨在确定干细胞的募集是否依赖趋化因子 SDF1,以及抑制同源受体 CXCR4 是否会影响肿瘤生长。
使用免疫荧光染色、BrdU 掺入和 eGFP 转基因小鼠来确定干细胞募集的动力学。使用 PCR 阵列鉴定趋化因子。使用 CXCR4 的抑制剂来确定对细胞迁移和肿瘤进展的影响。
随时间推移,在肿瘤球体中发现的干细胞数量增加归因于细胞招募。外源性 SDF1 增强了干细胞在体外的迁移,而 CXCR4 抑制和则消除了这种迁移。CXCR4 抑制减少了体内肿瘤负担。
SDF1 是招募干细胞到恶性腹膜间皮瘤的候选趋化因子,也是治疗的潜在靶点。