Zhuang Lei, Steinberg Florian, Trueb Beat
Department of Clinical Research, University of Bern, CH-3008 Bern, Switzerland.
Department of Clinical Research, University of Bern, CH-3008 Bern, Switzerland; Center for Biological Systems Analysis, University of Freiburg, D-79104 Freiburg, Germany.
Oncol Lett. 2016 Dec;12(6):4524-4530. doi: 10.3892/ol.2016.5245. Epub 2016 Oct 12.
Fibroblast growth factor receptor-like 1 (FGFRL1) is a transmembrane receptor that interacts with heparin and FGF ligands. In contrast to the classical FGF receptors, FGFR1 to FGFR4, it does not appear to affect cell growth and proliferation. In the present study, an inducible gene expression system was utilized in combination with a xenograft tumor model to investigate the effects of FGFRL1 on cell adhesion and tumor formation. It was determined that recombinant FGFRL1 promotes the adhesion of HEK 293 Tet-On cells . Moreover, when such cells are induced to express FGFRL1ΔC they aggregate into huge clusters. If injected into nude mice, the cells form large tumors. Notably, this tumor growth is completely inhibited when the expression of FGFRL1 is induced. The forced expression of FGFRL1 in the tumor tissue may restore contact inhibition, thereby preventing growth of the cells in nude mice. The results of the present study demonstrate that FGFRL1 acts as a tumor suppressor similar to numerous other cell adhesion proteins. It is therefore likely that FGFRL1 functions as a regular cell-cell adhesion protein.
成纤维细胞生长因子受体样1(FGFRL1)是一种与肝素和FGF配体相互作用的跨膜受体。与经典的FGF受体FGFR1至FGFR4不同,它似乎不影响细胞生长和增殖。在本研究中,诱导基因表达系统与异种移植肿瘤模型结合使用,以研究FGFRL1对细胞黏附和肿瘤形成的影响。已确定重组FGFRL1促进HEK 293 Tet-On细胞的黏附。此外,当此类细胞被诱导表达FGFRL1ΔC时,它们会聚集形成巨大的簇。如果将这些细胞注射到裸鼠体内,它们会形成大肿瘤。值得注意的是,当FGFRL1的表达被诱导时,这种肿瘤生长会被完全抑制。肿瘤组织中FGFRL1的强制表达可能会恢复接触抑制,从而阻止裸鼠体内细胞的生长。本研究结果表明,FGFRL1与许多其他细胞黏附蛋白类似,起到肿瘤抑制因子的作用。因此,FGFRL1很可能作为一种常规的细胞间黏附蛋白发挥作用。