| RRC ID |
72873
|
| 著者 |
Koizumi K, Shintani T, Hayashido Y, Hamada A, Higaki M, Yoshioka Y, Sakamoto A, Yanamoto S, Okamoto T.
|
| タイトル |
VEGF-A promotes the motility of human melanoma cells through the VEGFR1-PI3K/Akt signaling pathway.
|
| ジャーナル |
In Vitro Cell Dev Biol Anim
|
| 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, VEGF165 is the most abundant and responsible for VEGF-A biological potency. VEGF165 facilitated the migration of melanoma cells in both a chemotactic and chemokinetic manner, but cell proliferation was not affected by VEGF165. VEGF165 also induced the phosphorylation of Akt. In addition, VEGF165-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 VEGF165-induced cell migration. Moreover, wortmannin, an inhibitor of phosphatidylinositol-3 kinase (PI3K) in the PI3K/Akt pathway, suppressed VEGF165-induced Akt phosphorylation and VEGF165-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 VEGF165. Thus, the downregulation of signaling via VEGF-A/VEGFR1 might be an effective therapeutic approach that could prevent the progression of malignant melanoma.
|
| 巻・号 |
58(8)
|
| ページ |
758-770
|
| 公開日 |
2022-9-1
|
| DOI |
10.1007/s11626-022-00717-3
|
| PII |
10.1007/s11626-022-00717-3
|
| PMID |
35997849
|
| PMC |
PMC9550759
|
| MeSH |
Animals
Antibodies, Neutralizing / pharmacology
Cell Movement / genetics
Humans
Melanoma* / genetics
Oligonucleotides, Antisense / pharmacology
Phosphatidylinositol 3-Kinase / metabolism
Phosphatidylinositol 3-Kinase / pharmacology
Phosphatidylinositol 3-Kinases / metabolism
Phosphatidylinositols / pharmacology
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction
Vascular Endothelial Growth Factor A* / metabolism
Wortmannin / pharmacology
|
| IF |
1.665
|
| リソース情報 |
| ヒト・動物細胞 |
SK-MEL-28(RCB1930)
G-361(RCB0991)
C32TG(RCB1929) |
