Leukocyte‑associated immunoglobulin‑like receptor 1 promotes tumorigenesis in RCC

Jingushi,Kentaro; Uemura,Motohide; Nakano,Kosuke; Hayashi,Yujiro; Wang,Cong; Ishizuya,Yu; Yamamoto,Yoshiyuki; Hayashi,Takuji; Kinouchi,Toshiro; Matsuzaki,Kyosuke; Kato,Taigo; Kawashima,Atsunari; Ujike,Takeshi; Nagahara,Akira; Fujita,Kazutoshi; Ueda,Koji; Tsujikawa,Kazutake; Nonomura,Norio

doi:10.3892/or.2018.6875

Leukocyte‑associated immunoglobulin‑like receptor 1 promotes tumorigenesis in RCC

Authors:
- Kentaro Jingushi
- Motohide Uemura
- Kosuke Nakano
- Yujiro Hayashi
- Cong Wang
- Yu Ishizuya
- Yoshiyuki Yamamoto
- Takuji Hayashi
- Toshiro Kinouchi
- Kyosuke Matsuzaki
- Taigo Kato
- Atsunari Kawashima
- Takeshi Ujike
- Akira Nagahara
- Kazutoshi Fujita
- Koji Ueda
- Kazutake Tsujikawa
- Norio Nonomura
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Affiliations: Department of Therapeutic Urologic Oncology, Osaka University, Graduate School of Medicine, Suita, Osaka 565‑0871, Japan, Department of Urology, Osaka University, Graduate School of Medicine, Suita, Osaka 565‑0871, Japan, Project for Personalized Cancer Medicine, Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Koto‑ku, Tokyo 135‑8550, Japan, Laboratory of Molecular and Cellular Physiology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565‑0871, Japan
Published online on: November 20, 2018 https://doi.org/10.3892/or.2018.6875
Pages: 1293-1303

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Abstract

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults, responsible for approximately 90‑95% of cases. We previously reported a novel method that enables direct extraction of extracellular vesicles (EVs) from surgically resected viable tissues, yielding what we term tissue‑exudative extracellular vesicles (Te‑EVs). Quantitative LC/MS analysis identified 3,871 proteins in Te‑EVs, among which leukocyte‑associated immunoglobulin‑like receptor 1 (LAIR1) was highly enriched in tumor Te‑EVs. In the present study, we found that LAIR1 was significantly upregulated in clinical specimens of human RCC tumor tissues compared to that noted in adjacent non‑cancerous renal tissues as determined by quantitative PCR analysis. LAIR1 overexpression resulted in accelerated cell proliferation and tumor growth in RCC cells. Moreover, knockdown of LAIR1 using siRNA significantly inhibited cell proliferation in RCC cells. Mechanistically, LAIR1 upregulated the phosphorylation status of Akt, which in turn increased cell proliferation in RCC cells. In clinical RCC specimens, RCC patients with high LAIR1 mRNA expression showed poor progression‑free survival compared to those with low LAIR1 expression. These findings indicate that LAIR1 promotes tumorigenesis in RCC.

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