Tumor autocrine motility factor is an angiogenic factor hat stimulates endothelial cell motility.
Autocrine motility factor (AMF) is a type of tumor-secreted cytokine that primarily stimulates tumor cell motility via receptor-mediated signaling pathways and is thought to be connected to tumor progression and metastasis. Using in vivo models, we showed that critical neovascularization responded to a biological amount of AMF. This angiogenic activity was fixed by specific inhibitors against AMF. AMF stimulated in vitro motility of human umbilical vein endothelial cells (HUVECs), inducing the expression of cell surface AMF receptor localizing a single predominant perinuclear pattern closely correlated with its motile ability. AMF also elicited the formation of tube-like structures mimicking angiogenesis when HUVECs were grown in three-dimensional type I collagen gels. We further immunohistochemically detected AMF receptors on the surrounding sites of newborn microvessels. These findings suggest that AMF is a possible tumor progressive angiogenic factor which may act in a paracrine manner for the endothelial cells in the clinical neoplasm, and it will be a new target for anti-angiogenic treatment.
Funasaka
T
T
Department of Hygienics, Gifu Pharmaceutical University, Gifu, 502, Japan.
Haga
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A
Raz
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Nagase
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H
D043925:Angiogenesis Inducing Agents / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005956:Glucose-6-Phosphate Isomerase / Q000494:pharmacology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D060285:Receptors, Autocrine Motility Factor; D018121:Receptors, Cytokine / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D043925:Angiogenesis Inducing Agents; D018121:Receptors, Cytokine; C555000:AMFR protein, human; D060285:Receptors, Autocrine Motility Factor; D044767:Ubiquitin-Protein Ligases; D005956:Glucose-6-Phosphate Isomerase