Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas
Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine/paracrine cell proliferation in human pituitary adenomas
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DOI：
10.1158/1078-0432.ccr-07-4717
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发表时间：
2008-08-15
影响因子：
11.5
通讯作者：
Florio, Tullio
中科院分区：
文献类型：
--
作者：
Barbieri, Federica;Bajetto, Adriana;Florio, Tullio
目的：下丘脑或局部产生的生长因子和细胞因子控制垂体发育、功能和细胞分裂。我们评估了趋化因子基质细胞衍生因子1（SDF 1）及其受体CXCR 4在人垂体腺瘤和正常垂体组织中的表达及其在细胞增殖中的作用。实验设计：SDF 1和CXCR 4在65例人垂体腺瘤和4例人正常垂体中的表达通过逆转录-PCR，免疫组化和共聚焦免疫荧光法测定。结果：CXCR 4 mRNA在92%的生长激素（GH）分泌型垂体腺瘤（GH oma）和81%的无功能垂体腺瘤（NFPA）中表达，而SDF 1在GH oma和NFPA中的表达率分别为63%和78%。CXCR 4和SDF 1的免疫染色显示在GHoma和NFPA中的所有肿瘤细胞中都有强烈的均匀标记。在正常组织中，CXCR 4和SDF 1仅在垂体前叶细胞亚群中表达，与其同源受体相比，SDF 1的表达较低。CXCR 4和SDF 1并不局限于垂体前叶的特定细胞群，而是与GH、催乳素和促肾上腺皮质激素分泌细胞的离散亚群共定位。相反，大多数含有SDF 1的细胞表达CXCR 4。在8个垂体腺瘤的原代培养物中，SDF 1诱导的DNA合成的增加是由CXCR 4拮抗剂AMD 3100或somatostatin.Conclusions治疗预防的，具有统计学意义：CXCR 4和SDF 1在人类垂体腺瘤和CXCR 4激活过表达可能有助于垂体细胞增殖，并可能，在人类腺瘤的发展。
Purpose: Hypothalamic or locally produced growth factors and cytokines control pituitary development, functioning, and cell division. We evaluated the expression of the chemokine stromal cell-derived factor 1 (SDF1) and its receptor CXCR4 in human pituitary adenomas and normal pituitary tissues and their role in cell proliferation.Experimental Design: The expression of SDF1 and CXCR4 in 65 human pituitary adenomas and 4 human normal pituitaries was determined by reverse transcription-PCR, immunohistochemistry, and confocal immunofluorescence. The proliferative effect of SDF1 was evaluated in eight fibroblast-free human pituitary adenoma cell cultures.Results: CXCR4 mRNA was expressed in 92% of growth hormone (GH)-secreting pituitary adenomas (GHoma) and 81% of nonfunctioning pituitary adenomas (NFPA), whereas SDF1 was identified in 63% and 78% of GHomas and NFPAs, respectively. Immunostaining for CXCR4 and SDF1 showed a strong homogenous labeling in all tumoral cells in both GHomas and NFPAs. In normal tissues, CXCR4 and SDF1 were expressed only in a subset of anterior pituitary cells, with a lower expression of SDF1 compared with its cognate receptor. CXCR4 and SDF1 were not confined to a specific cell population in the anterior pituitary but colocalized with discrete subpopulations of GH-, prolactin-, and adrenocorticorticotropic hormone-secreting cells. Conversely, most of the SDF1-containing cells expressed CXCR4. In six of eight pituitary adenoma primary cultures, SDF1 induced a statistically significant increase in DNA synthesis that was prevented by the treatment with the CXCR4 antagonist AMD3100 or somatostatin.Conclusions: CXCR4 and SDF1 are overexpressed in human pituitary adenomas and CXCR4 activation may contribute to pituitary cell proliferation and, possibly, to adenoma development in humans.