Stromal cell-derived factor-1 expression in pituitary adenoma tissues and upregulation in hypoxia
Stromal cell-derived factor-1 expression in pituitary adenoma tissues and upregulation in hypoxia
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DOI：
10.1007/s11060-009-9835-2
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发表时间：
2009-09-01
影响因子：
3.9
通讯作者：
Teramoto, Akira
中科院分区：
文献类型：
--
作者：
Nomura, Ryutaro;Yoshida, Daizo;Teramoto, Akira
已知趋化因子基质细胞衍生因子-1（SDF-1/CXCL 12）具有归巢效应，将内皮祖细胞（EPCs）从骨髓募集到缺血灶。在这项研究中，我们研究了SDF-1是否由缺氧触发，并可能是垂体腺瘤中肿瘤血管生成的主要驱动力。应用免疫荧光双标法检测59例垂体腺瘤中CD 34阳性血管中SDF-1和微血管密度（MVD）。在体外分泌SDF-1的AtT 20小鼠垂体腺瘤细胞系在缺氧条件下进行了定量分析，SDF-1的mRNA水平，通过实时RT-PCR测定。双荧光免疫组化显示MVD的增加与SDF-1分级的增加显著相关（P < 0.0001），同时，SDF-1在大腺瘤中的表达显著增加（P = 0.0203）。SDF-1分泌与氧水平呈负相关，缺氧程度越严重，SDF-1分泌水平越高。Real-time RT-PCR结果显示，与21%氧相比，1%氧时AtT 20细胞中SDF-1 mRNA的表达量显著增加（对数平均值= 1.55 +/-A0.56）。目前的研究强烈表明，SDF-1是一个重要的血管生成因子在垂体腺瘤，它作为一个归巢剂介导动员CD 34阳性内皮祖细胞的肿瘤实质在缺氧条件下。
The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) is known to have a homing effect, recruiting endothelial progenitor cells (EPCs) from the bone marrow to ischemic foci. In this study, we investigated whether SDF-1 is triggered by hypoxia and might be a major driving force for tumor angiogenesis in pituitary adenomas. SDF-1 and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from 59 cases with pituitary adenomas. In vitro secretion of SDF-1 by the AtT20 mouse pituitary adenoma cell line under hypoxic conditions was quantitatively analyzed by ELISA, and SDF-1 mRNA levels were determined by real-time RT-PCR. Double-fluorescence immunohistochemistry showed that increases in MVD were significantly correlated with increased SDF-1 grade (P < 0.0001), and, concomitantly, the expression of SDF-1 was significantly greater in macroadenomas (P = 0.0203). SDF-1 secretion was inversely related to oxygen levels, with more severe degrees of hypoxia inducing greater levels of SDF-1 secretion. Real-time RT-PCR demonstrated that the SDF-1 mRNA level in AtT20 cells was significantly increased at 1% oxygen (logarithmic mean value = 1.55 +/- A 0.56) compared with that at 21% oxygen. The current study strongly suggests that SDF-1 is a crucial angiogenic factor in pituitary adenomas, where it acts as a homing agent to mediate the mobilization of CD34-positive endothelial progenitor cells to the tumor parenchyma under hypoxic conditions.