Department of Neurosurgery, Nippon Medical School, Tokyo 113-8602, Japan.
Int J Endocrinol. 2015;2015:834137. doi: 10.1155/2015/834137. Epub 2015 Mar 5.
Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P < 0.005, r (2) = 0.4958). In contrast, Gremlin expression showed no correlation with tumor subtype or Knosp score. The high level of expression of Gremlin in pituitary adenoma tissue with many CD34-positive vessels and the strong coherence of these regions indicate that Gremlin is associated with angiogenesis in pituitary adenoma cells.
Gremlin 是骨形态发生蛋白 (BMP) 的拮抗剂，也是胎儿阶段骨骼建模的主要驱动力。最近的几项报告表明，Gremlin 也参与了肺癌和糖尿病性视网膜病变的血管生成。本研究旨在探讨 Gremlin 在垂体腺瘤肿瘤血管生成中的作用。对 45 例经蝶窦手术获得的垂体腺瘤组织进行了 Gremlin 和 CD34 的双重荧光免疫组织化学染色（7 例泌乳素瘤、17 例生长激素瘤、2 例 ACTH 瘤和 2 例 TSH 瘤）。通过 CD34 阳性血管的双重免疫荧光显微镜检测了 60 例垂体腺瘤组织的组织微阵列分析中的 Gremlin 和微血管密度 (MVD)（6 例泌乳素瘤、23 例生长激素瘤、22 例无功能腺瘤、5 例 ACTH 瘤和 4 例 TSH 瘤）。在组织微阵列分析中，MVD 与 Gremlin 水平的升高呈显著相关（线性回归：P < 0.005，r (2) = 0.4958）。相比之下，Gremlin 的表达与肿瘤亚型或 Knosp 评分无关。在富含 CD34 阳性血管的垂体腺瘤组织中 Gremlin 表达水平较高，且这些区域之间具有很强的一致性，这表明 Gremlin 与垂体腺瘤细胞的血管生成有关。
