EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) AND ITS RECEPTORS IN BREAST-CANCER
EXPRESSION OF VASCULAR-PERMEABILITY FACTOR (VASCULAR ENDOTHELIAL GROWTH-FACTOR) AND ITS RECEPTORS IN BREAST-CANCER
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DOI：
10.1016/0046-8177(95)90119-1
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发表时间：
1995-01-01
期刊：
影响因子：
3.3
通讯作者：
SCHNITT, SJ
中科院分区：
文献类型：
--
作者：
BROWN, LF;BERSE, B;SCHNITT, SJ
实体瘤必须诱导血管基质生长超过最小尺寸，并且血管生成反应的强度与乳腺癌患者的预后相关。血管通透性因子（VPF），也称为血管内皮生长因子（VEGF），是一种分泌性蛋白，与肿瘤相关的血管生成有关。血管通透性因子直接刺激内皮细胞生长，也增加微血管通透性，导致血浆蛋白外渗，从而以促进血管生成的方式改变细胞外基质。为了确定VPF是否在乳腺癌中发挥作用，我们采用原位杂交技术研究了VPF mRNA在正常乳腺组织（13例）、粉刺型导管原位癌（DCIS）（4例）、浸润性导管癌（12例）、浸润性小叶癌（2例）、转移性导管癌（3例）和转移性小叶癌（1例）中的表达。血管通透性因子mRNA在正常导管上皮中表达较低，但在所有粉刺型DCIS、浸润性导管癌和转移性导管癌的肿瘤细胞中表达较高。相反，VPF mRNA在浸润性小叶癌中不高水平表达。我们还使用原位杂交研究了两种最近描述的内皮细胞表面VPI的表达：受体flt-1和kdr。血管通透性因子受体mRNA在DCIS、浸润性导管癌和转移性导管癌中与恶性肿瘤细胞相邻的小血管内皮细胞中强表达。相反，在浸润性小叶癌或非恶性乳腺组织中未检测到明确的受体mRNA标记。乳腺癌细胞VPF mRNA和邻近小血管内皮细胞VPF受体mRNA的强烈表达提供了强有力的证据，将VPF表达与粉刺型DCIS、浸润性导管和转移性导管乳腺癌相关的血管生成联系起来。《人文哲学》26：86-91。版权所有（C）1995由W.B.桑德斯公司
Solid tumors must induce a vascular stroma to grow beyond a minimal size, and the intensity of the angiogenic response has been correlated with prognosis in breast cancer patients. Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a secreted protein that has been implicated in tumor-associated angiogenesis. Vascular permeability factor directly stimulates endothelial cell growth and also increases microvascular permeability, leading to the extravasation of plasma proteins, which alter the extracellular matrix in a manner that promotes angiogenesis. To determine whether VPF has a role in breast cancer, we used in situ hybridization to study VPF mRNA expression in normal breast tissue (13 specimens), comedo-type ductal carcinoma in situ (DCIS) (four specimens), infiltrating ductal carcinoma (12 specimens), infiltrating lobular carcinoma (two specimens), metastatic ductal carcinoma (three specimens) and metastatic lobular carcinoma (one specimen). Vascular permeability factor mRNA Has expressed at a low level by normal duct epithelium but was expressed at high levels in tumor cells in all cases of comedo-type DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, VPF mRNA was not expressed at high levels in infiltrating lobular carcinoma. We also used in situ hybridization to study the expression of two recently described endothelial cell surface VPI: receptors, flt-1 and kdr. Vascular permeability factor receptor mRNA was strongly expressed in endothelial cells of small vessels adjacent to malignant tumor cells in DCIS, infiltrating ductal carcinoma, and metastatic ductal carcinoma. In contrast, no definite labeling for receptor mRNA was detected in infiltrating lobular carcinoma or nonmalignant breast tissue. The intense expression of VPF mRNA by breast carcinoma cells and of VPF receptor mRNA by endothelial cells of adjacent small blood vessels provides strong evidence linking VPF expression to the angiogenesis associated with comedo-type DCIS, infiltrating ductal, and metastatic ductal breast carcinoma. HUM PATHOL 26:86-91. Copyright (C) 1995 by W.B. Saunders Company