Leukocyte-associated immunoglobulin-like receptor 1 promotes tumorigenesis in RCC
Leukocyte-associated immunoglobulin-like receptor 1 promotes tumorigenesis in RCC
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DOI：
10.3892/or.2018.6875
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发表时间：
2019-02-01
期刊：
影响因子：
4.2
通讯作者：
Nonomura, Norio
中科院分区：
文献类型：
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作者：
Jingushi, Kentaro;Uemura, Motohide;Nonomura, Norio
肾细胞癌（RCC）是成人中最常见的肾癌类型，约占90-95%的病例。我们以前报道了一种新的方法，使直接提取细胞外囊泡（EV）从手术切除的活组织，产生我们所谓的组织渗出性细胞外囊泡（Te-EV）。定量LC/MS分析在Te-EV中鉴定了3，871种蛋白质，其中白细胞相关免疫球蛋白样受体1（LAIR 1）在肿瘤Te-EV中高度富集。在本研究中，我们发现，LAIR 1是显着上调的临床标本中的人RCC肿瘤组织相比，注意到在相邻的非癌肾组织，如通过定量PCR分析确定。LAIR 1过表达导致RCC细胞中细胞增殖和肿瘤生长加速。此外，使用siRNA敲低LAIR 1显著抑制RCC细胞中的细胞增殖。从机制上讲，LAIR 1上调Akt的磷酸化状态，这反过来又增加了RCC细胞的细胞增殖。在临床RCC标本中，LAIR 1 mRNA高表达的RCC患者的无进展生存率低于LAIR 1低表达的患者。这些发现表明LAIR 1促进RCC中的肿瘤发生。
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.