Chen Dai-lun, Ping Yi-fang, Yu Shi-cang, Chen Jian-hong, Yao Xiao-hong, Jiang Xue-feng, Zhang Hua-rong, Wang Qing-liang, Bian Xiu-wu
Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Biochem Biophys Res Commun. 2009 Apr 10;381(3):448-52. doi: 10.1016/j.bbrc.2009.02.065. Epub 2009 Feb 20.
G-protein-coupled formylpeptide receptor (FPR) has recently been found to be functionally expressed in gliomas and are probably involved in their malignant biological behavior. In an attempt to explore the therapeutic significance of FPRs, we used wild-type human glioblastoma cells (U87), the corresponding FPR short-interfering RNA transfected (siRNA U87) cells, and mock-transfected U87 cells (mock U87) to establish xenografts in mice brains. Compared to wild-type and mock transfected cells, siRNA U87 cells formed smaller and more well-differentiated xenografts with fewer mitotic figures and more glial filaments within their cytoplasm. The density of microvessels, which presented as a nearly normal morphous, was also decreased significantly in FPR knockdown cells. Moreover, fewer invasive foci could be observed in the xenografts derived from siRNA U87 cells, which also showed a poor migratory capacity in vitro. We suggest that decreased VEGF and MMP-2/-9 expression might be a possible mechanism for the decreasing angiogenic potential and invasive capability of U87 cells after FPR knockdown. Functional FPR might be essential for sustaining the growth and aggressive phenotype of gliomas, and could therefore be a potential therapeutic target.
G蛋白偶联甲酰肽受体（FPR）最近被发现在胶质瘤中功能性表达，可能参与其恶性生物学行为。为了探索FPR的治疗意义，我们使用野生型人胶质母细胞瘤细胞（U87）、相应的FPR短发夹RNA转染（siRNA U87）细胞和mock转染的U87细胞（mock U87）在小鼠脑内建立异种移植瘤。与野生型和mock转染细胞相比，siRNA U87细胞形成的异种移植瘤更小且分化更好，有丝分裂象更少，细胞质内有更多的胶质纤维。呈现出近乎正常形态的微血管密度在FPR敲低细胞中也显著降低。此外，在源自siRNA U87细胞的异种移植瘤中观察到的侵袭灶更少，其在体外也显示出较差的迁移能力。我们认为VEGF和MMP - 2/-9表达降低可能是FPR敲低后U87细胞血管生成潜力和侵袭能力下降的一种可能机制。功能性FPR可能对维持胶质瘤的生长和侵袭性表型至关重要，因此可能是一个潜在的治疗靶点。
