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.
Oncol Rep. 2019 Feb;41(2):1293-1303. doi: 10.3892/or.2018.6875. Epub 2018 Nov 20.
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.
肾细胞癌 (RCC) 是成人中最常见的肾癌类型,约占 90-95%的病例。我们之前报道了一种从手术切除的活组织中直接提取细胞外囊泡 (EVs) 的新方法,得到了我们称之为组织渗出性细胞外囊泡 (Te-EVs)。定量 LC/MS 分析在 Te-EVs 中鉴定出 3871 种蛋白质,其中白细胞相关免疫球蛋白样受体 1 (LAIR1) 在肿瘤 Te-EVs 中高度富集。在本研究中,我们发现与相邻非癌性肾组织相比,LAIR1 在人 RCC 肿瘤组织的临床标本中显著上调,这是通过定量 PCR 分析确定的。LAIR1 的过表达导致 RCC 细胞的增殖和肿瘤生长加速。此外,使用 siRNA 敲低 LAIR1 显著抑制了 RCC 细胞的增殖。在机制上,LAIR1 上调了 Akt 的磷酸化状态,从而增加了 RCC 细胞的增殖。在临床 RCC 标本中,LAIR1 mRNA 表达水平高的 RCC 患者与 LAIR1 低表达的患者相比,无进展生存期较差。这些发现表明 LAIR1 促进了 RCC 的肿瘤发生。