Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features
Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features
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DOI：
10.1016/s0002-9440(10)65515-0
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发表时间：
1999-12-01
影响因子：
6
通讯作者：
Bongarzone, I
中科院分区：
文献类型：
--
作者：
Bunone, G;Vigneri, P;Bongarzone, I
在体外和动物模型中，实验证据表明，肿瘤生长和随后的转移形成取决于肿瘤诱导血管生成转换的能力。这需要改变血管生成刺激物和抑制物的平衡。为了评估血管生成因子在人类甲状腺肿瘤生长和扩散中的潜在作用，我们通过半定量RT-PCR和免疫组织化学分析了它们在正常甲状腺组织、良性病变和不同甲状腺癌中的表达。与正常组织相比，在甲状腺肿瘤中，我们观察到血管内皮生长因子（VEGF）、VEGF-C和血管生成素-2及其酪氨酸激酶受体KDR的一致增加，Flt-4和Tek，特别是，我们报告了血管生成素-2和VEGF在甲状腺肿瘤从血管前阶段进展到血管阶段中的过表达。事实上，我们发现肿瘤大小和高水平的VEGF和血管生成素-2之间存在很强的相关性。此外，我们的研究结果表明，VEGF-C在淋巴结浸润性甲状腺肿瘤中的表达增加，另一方面，在能够血液扩散的甲状腺恶性肿瘤中，血小板反应蛋白-lr一种血管抑制因子的表达减少。这些结果表明，在人类甲状腺肿瘤中，血管生成因子似乎参与肿瘤生长和侵袭性。此外，我们的研究结果与最近的一个假设一致，即在VEGF存在的情况下，血管生成素-2可能在入侵的血管芽的前部合作，作为伴随肿瘤生长的初始血管生成信号。
Experimental evidence has shown, both in vitro and in animal models, that neoplastic growth and subsequent metastasis formation depend on the tumor's ability to induce an angiogenic switch, This requires a change in the balance of angiogenic stimulators and inhibitors. To assess the potential role of angiogenesis factors in human thyroid tumor growth and spread, we analyzed their expression by semiquantitative RT-PCR and immunohistochemistry in normal thyroid tissues, benign lesions, and different thyroid carcinomas, Compared to normal tissues, in thyroid neoplasias we observed a consistent increase in vascular endothelial growth factor (VEGF), VEGF-C, and angiopoietin-2 and in their tyrosine kinase receptors KDR, Flt-4, and Tek, In particular, we report the overexpression of angiopoietin-2 and VEGF in thyroid tumor progression from a prevascular to a vascular phase. In fact, we found a strong association between tumor size and high levels of VEGF and angiopoietin-2, Furthermore, our results show an increased expression of VEGF-C in lymph node invasive thyroid tumors and, on the other hand, a decrease of thrombospondin-lr an angioinhibitory factor, in thyroid malignancies capable of hematic spread. These results suggest,that, in human thyroid tumors, angiogenesis factors seem involved in neoplastic growth and aggressiveness. Moreover, our findings are in keeping with a recent hypothesis that in the presence of VEGF, angiopoietin-2 may collaborate at the front of invading vascular sprouts, serving as an initial angiogenic signal that accompanies tumor growth.