Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells.

Receptor FGFRL1 acts as a tumor suppressor in nude mice when overexpressed in HEK 293 Tet-On cells.
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DOI:
10.3892/ol.2016.5245
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发表时间:
2016-12
期刊:
影响因子:
2.9
通讯作者:
Trueb B
Trueb B
中科院分区:
医学4区
文献类型:
--
作者:
Zhuang L;Steinberg F;Trueb B

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成纤维细胞生长因子受体样1(FGFRL 1)是与肝素和FGF配体相互作用的跨膜受体。与经典的FGF受体FGFR 1至FGFR 4相反,它似乎不影响细胞生长和增殖。在本研究中,诱导型基因表达系统与异种移植肿瘤模型结合使用,以研究FGFRL 1对细胞粘附和肿瘤形成的影响。已确定重组FGFRL 1在体外促进HEK 293 Tet-On®细胞的粘附。此外,当这些细胞被诱导表达FGFRL 1 ΔC时,它们聚集成巨大的簇。如果注射到裸鼠体内,这些细胞会形成大肿瘤。值得注意的是,当FGFRL 1的表达被诱导时,这种肿瘤生长被完全抑制。在肿瘤组织中强制表达FGFRL 1可以恢复接触抑制,从而阻止细胞在裸鼠中的生长。本研究的结果表明,FGFRL 1作为一种肿瘤抑制剂类似于许多其他细胞粘附蛋白。因此,FGFRL 1可能作为常规的细胞-细胞粘附蛋白发挥作用。
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 in vitro. 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.