NRP1 knockdown promotes the migration and invasion of human neuroblastoma-derived SK‑N‑AS cells via the activation of β1 integrin expression

Ishizuka,Yoshiaki; Koshinaga,Tsugumichi; Hirano,Takayuki; Nagasaki‑Maeoka,Eri; Watanabe,Yosuke; Hoshi,Reina; Yoshizawa,Shinsuke; Sugito,Kiminobu; Kawashima,Hiroyuki; Uekusa,Shota; Fukuda,Noboru; Soma,Masayoshi; Fujiwara,Kyoko

doi:10.3892/ijo.2018.4397

NRP1 knockdown promotes the migration and invasion of human neuroblastoma-derived SK‑N‑AS cells via the activation of β1 integrin expression

Authors:
- Yoshiaki Ishizuka
- Tsugumichi Koshinaga
- Takayuki Hirano
- Eri Nagasaki‑Maeoka
- Yosuke Watanabe
- Reina Hoshi
- Shinsuke Yoshizawa
- Kiminobu Sugito
- Hiroyuki Kawashima
- Shota Uekusa
- Noboru Fukuda
- Masayoshi Soma
- Kyoko Fujiwara
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Affiliations: Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan, Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan, Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo 173-8610, Japan
Published online on: May 7, 2018 https://doi.org/10.3892/ijo.2018.4397
Pages: 159-166

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Abstract

Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which regulates many aspects of cellular function by functioning as co-receptor of various ligands. Recent studies have suggested that NRP1 promotes tumorigenesis, not only by activating the growth of tumor vessels, but also by activating the growth or migration of tumor cells themselves. The present study was performed to elucidate the roles of NRP1 in the development and/or progression of neuroblastoma (NB). In contrast to previous observations in various types of cancer, the analysis of public datasets indicated that lower levels of NRP1 expression were significantly associated with a shorter survival period of patients with NB. Consistent with this finding, wound-healing assay and Matrigel invasion assay revealed that NB cells in which NRP1 was knocked down exhibited increased migratory and invasive abilities. Further analyses indicated that β1 integrin expression was markedly increased in NB cells in which NRP1 was knocked down, and NB cells in which β1 integrin was knocked down exhibited decreased migratory and invasive abilities. The results presented herein indicate that NRP1 exerts tumor suppressive effects in NB, at least in part by regulating the expression of β1 integrin.

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