Department of Oncology Clinical Development, Gunma University Graduate School of Medicine Showa-machi, Maebashi, Gunma, Japan.
Department of Surgery, Maebashi Red Cross Hospital Asahi-cho, Maebashi, Gunma, Japan.
Am J Transl Res. 2015 Feb 15;7(2):356-63. eCollection 2015.
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.
CD147 作为基质金属蛋白酶和肿瘤血管生成的诱导因子，在各种恶性肿瘤中高度表达。最近，CD147 被证明与氨基酸转运体如 L 型氨基酸转运体（LAT1）、系统 ASC 氨基酸转运体-2（ASCT2）和 4F2hc 形成复合物，作为 LAT1 的重链。这些复合物在胰腺癌患者中是否存在尚不清楚。本研究旨在探讨 CD147 与这些氨基酸转运体之间的关系。评估了 97 例胰腺癌患者。肿瘤切片通过免疫组织化学染色检测 LAT1、ASCT2、Ki-67、CD34 确定的微血管密度（MVD）、p-AKT 和 p-mTOR。23%（22/97）的患者 CD147 高表达。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 高表达是一个显著的预后预测因子。CD147 与 LAT1 的共表达，以及与 4F2hc 的共表达，与 LAT1 和 4F2hc 的单表达相比，预后明显更差。CD147 与 LAT1 和 ASCT2 的表达水平显著相关，与肿瘤增殖、血管生成和 mTOR 信号相关。
