Relationship between CD 147 and expression of amino acid transporters ( LAT 1 and ASCT 2 ) in patients with pancreatic cancer
Relationship between CD 147 and expression of amino acid transporters ( LAT 1 and ASCT 2 ) in patients with pancreatic cancer
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
K. Kaira;K. Arakawa;K. Shimizu;N. Oriuchi;S. Nagamori;Y. Kanai;T. Oyama;I. Takeyoshi
中科院分区：
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作者：
K. Kaira;K. Arakawa;K. Shimizu;N. Oriuchi;S. Nagamori;Y. Kanai;T. Oyama;I. Takeyoshi
CD147具有诱导基质金属蛋白酶和肿瘤血管生成的作用，在多种恶性肿瘤中均有高表达。最近发现CD147作为LAT1的重链与L氨基酸转运体(LAT1)、系统ASC氨基酸转运体2(ASCT2)和4F2hc等氨基酸转运体形成复合体。目前尚不清楚胰腺癌患者体内是否存在这些复合体。本研究旨在探讨CD147与这些氨基酸转运体之间的关系。我们对97例胰腺癌患者进行了评估。肿瘤切片采用免疫组织化学LAT1、ASCT2、Ki-67染色，CD34、p-AKT、p-mTOR检测微血管密度(MVD)。CD147高表达者占23%(22/97)。CD147的高表达与N因子、LAT1、ASCT2、Ki-67、VEGF和p-mTOR显著相关。单因素生存分析表明，CD147的高表达是一个显著的预后预测因素。CD147和LAT1、CD147和4F2hc共同表达的预后分别比单独表达LAT1和4F2hc的预后差。CD147与LAT1、ASCT2的表达水平呈正相关，与肿瘤增殖、血管生成及mTOR信号转导有关。
CD147 functions as an induction of matrix metalloproteinases and tumor angiogenesis, and is highly expressed in various malignant neoplasms. Recently, CD147 is shown to form a complex with amino acid transporters such as L-type amino acid transporter (LAT1), system ASC amino acid transporter-2 (ASCT2) and 4F2hc as a heavy chain of LAT1. It remains unknown about the existence of these complexes in patients with pancreatic cancer. The aim of this study is to investigate the relationship between CD147 and these amino acid transporters. Ninety-seven patients with pancreatic cancer were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, ASCT2, Ki-67, microvessel density (MVD) determined by CD34, p-AKT, and p-mTOR. CD147 was highly expressed in 23% (22/97) of patients. A high expression of CD147 is significantly associated with N factor, LAT1, ASCT2, Ki-67, VEGF and p-mTOR. A high CD147 expression was identified as a significant prognostic predictor by univariate survival analysis. The coexpression of CD147 and LAT1, and that of CD147 and 4F2hc yielded a significantly worse prognosis than the single expression of LAT1, and that of 4F2hc, respectively. CD147 revealed a significant relationship with the expression level of LAT1 and ASCT2, correlated with tumor proliferation, angiogenesis and mTOR signaling.