Funasaka Tatsuyoshi, Haga Arayo, Raz Avraham, Nagase Hisamitsu
Department of Hygienics, Gifu Pharmaceutical University, Japan.
Int J Cancer. 2002 Sep 20;101(3):217-23. doi: 10.1002/ijc.10617.
The autocrine motility factor (AMF) is known as a cytokine regulating tumor cells motility via AMF receptor (AMFR) and promotes their metastasis. Recently, AMFRs have been found on the surface of host cells and it was showed that AMF possibly affects them. The signaling of AMF-AMFR in the host endothelial cells induces expression of a vascular endothelial growth factor receptor (VEGFR) Flt-1 and AMFR feedback that is regulated at the transcriptional level. AMF-exposure stimulated the Flt-1 expression on human umbilical vein endothelial cells (HUVECs) surface and this AMF-treated cells exhibited high-responsibility against VEGF. The protein kinase C (PKC) and phosphatidylinositol 3 kinase (PI3K) play an important role in this signal transduction. The findings of our study suggest the possibility of "tumor AMF-->host AMFR-->PKC, PI3K-->-->VEGFR or AMFR-->angiogenesis, metastasis" as a new signal cross talk between the tumor and the host.
自分泌运动因子（AMF）是一种通过AMF受体（AMFR）调节肿瘤细胞运动的细胞因子，并促进其转移。最近，在宿主细胞表面发现了AMFR，并且有研究表明AMF可能会对其产生影响。宿主内皮细胞中AMF-AMFR信号通路可诱导血管内皮生长因子受体（VEGFR）Flt-1的表达以及在转录水平受到调控的AMFR反馈。AMF暴露刺激了人脐静脉内皮细胞（HUVECs）表面Flt-1的表达，并且这些经AMF处理的细胞对VEGF表现出高反应性。蛋白激酶C（PKC）和磷脂酰肌醇3激酶（PI3K）在该信号转导中起重要作用。我们的研究结果提示了“肿瘤AMF→宿主AMFR→PKC、PI3K→→VEGFR或AMFR→血管生成、转移”作为肿瘤与宿主之间新的信号串扰的可能性。
