VEGF-A promotes the motility of human melanoma cells through the VEGFR1--PI3K/Akt signaling pathway.

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Publisher: Springer
Document Type: Report; Brief article
Length: 297 words

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Keywords: Melanoma; Cell motility; VEGF-A; VEGFR1; PI3K/Akt signaling pathway Abstract Vascular endothelial growth factor A (VEGF-A) and its receptors (VEGFR1 and R2) play important roles in the progression of malignant melanoma through tumor angiogenesis. However, it is not clear whether the VEGF-A/VEGFR1 signaling pathway is involved in the proliferation and migration of melanoma cells. Thus, the effect of VEGF-A on cell migration was investigated in human melanoma cell lines. Of several splicing variants of VEGF-A, VEGF.sub.165 is the most abundant and responsible for VEGF-A biological potency. VEGF.sub.165 facilitated the migration of melanoma cells in both a chemotactic and chemokinetic manner, but cell proliferation was not affected by VEGF.sub.165. VEGF.sub.165 also induced the phosphorylation of Akt. In addition, VEGF.sub.165-induced cell migration was inhibited significantly by VEGFR1/2 or a VEGFR1-neutralizing antibody. Furthermore, the downregulation of VEGFR1 via the transfection of VEGFR1-targeting antisense oligonucleotides suppressed VEGF.sub.165-induced cell migration. Moreover, wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI3K) in the PI3K/Akt pathway, suppressed VEGF.sub.165-induced Akt phosphorylation and VEGF.sub.165-induced cell migration. These findings suggest that the motility of melanoma cells is regulated by signals mediated through the PI3K/Akt kinase pathway with the activation of VEGFR1 tyrosine kinase by VEGF.sub.165. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma. Author Affiliation: (1) Department of Oral Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 734-8553, Hiroshima, Japan (2) Center of Oral Clinical Examination, Hiroshima University Hospital, 734-8551, Hiroshima, Japan (3) Oral Maxillofacial Surgery, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, 734-8551, Hiroshima, Japan (4) Oral Maxillofacial Surgery, Hiroshima University Hospital, 734-8551, Hiroshima, Japan (5) School of Medical Sciences, University of East Asia, 751-8503, Shimonoseki, Japan (c) Article History: Registration Date: 08/15/2022 Received Date: 07/13/2022 Accepted Date: 08/12/2022 Online Date: 08/23/2022 Byline:

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Gale Document Number: GALE|A721886639