Autocrine motility factor secreted by tumor cells upregulates vascular endothelial growth factor receptor (Flt‐1) expression in endothelial cells

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Abstract
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.