Tumor growth of FGF or VEGF transfected MCF-7 breast carcinoma cells correlates with density of specific microvessels independent of the transfected angiogenic factor
Tumor growth of FGF or VEGF transfected MCF-7 breast carcinoma cells correlates with density of specific microvessels independent of the transfected angiogenic factor
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DOI：
10.1016/s0002-9440(10)65713-6
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发表时间：
1998-12-01
影响因子：
6
通讯作者：
Hanfelt, J
中科院分区：
文献类型：
--
作者：
McLeskey, SW;Tobias, CA;Hanfelt, J
我们先前已经证明，成纤维细胞生长因子-1、成纤维细胞生长因子-4或血管内皮细胞生长因子(VEGF/VPF)转导的MCF-7乳腺癌细胞在裸鼠体内生长为肿瘤，对他莫昔芬耐药和/或雌激素非依赖性。这些转染体为研究在促进生长和抑制生长的激素条件下由单个血管生成因子促进的原位肿瘤血管生成提供了机会。在本研究中，通过盲目观察者对注射肿瘤细胞后不同时间采集的肿瘤中的血管进行了免疫组织化学强调，并对血管形态和地形图进行了0到4分的评分。在所有促进生长的激素条件下，所有细胞系产生的肿瘤中，与生长抑制条件下采集的肿瘤结节相比，边缘相关和肿瘤内微血管的丰度显著增加(P<；0.05)，但间质微血管的丰度没有显著增加(P<；0.05)，无论血管生成因子或激素治疗的特性如何。对所有细胞系在早期时间点采集的所有激素条件下产生的肿瘤细胞核进行的图像分析显示，在特定细胞系中产生最强劲生长的激素条件下，平均标记指数最高，这意味着高BrdU标记指数是单个肿瘤未来肿瘤生长的预测指标。这些结果证实了先前的研究，证实了新生血管对肿瘤生长的重要性，并为利用这些细胞系研究体内血管生成过程提供了验证，利用该模型研究边缘相关血管或肿瘤内血管内皮细胞的基因表达可能揭示肿瘤诱导乳腺癌血管生成的重要机制。
We have previously shown that fibroblast growth factor (FGF)-1-, FGF-4-, or vascular endothelial growth factor (VEGF/VPF)-transfected MCF-7 breast carcinoma cells growing as tumors in nude mice are tamoxifen resistant and/or estrogen independent. These transfectants provide opportunity for study of in situ tumor-induced angiogenesis promoted by the individual angiogenic factors under growth-promoting versus growth-inhibiting hormonal conditions. In the present study, vessels in tumors harvested at varying times after tumor cell injection were immunohistochemically highlighted and vessel morphology and topography were scored on a scale of 0 to 4 by blinded observers, In tumors produced by all cell Lines under all growth-promoting hormonal conditions, there was significantly increased abundance (P < 0.05) of edge-associated and intratumor microvessels, but not of stromally located microvessels, when compared with tumor nodules harvested under growth-inhibiting conditions, regardless of the identity of the angiogenic factor or the hormonal treatment. Image analysis of bromodeoxyuridine (BrdU)-labeled nuclei of tumors produced by all cell Lines under all hormonal conditions harvested at early time points showed that mean labeling indices were highest for hormonal conditions that produced the most robust growth in that particular cell line, implying that a high BrdU labeling index is a predictor of future tumor growth in individual tumors. These results confirm previous studies that established the importance of neovascularization for tumor growth and provide validation for use of these cell lines to study the process of angiogenesis in vivo, Study of gene expression in endothelial cells in edge-associated or intratumor vessels using this model might reveal mechanisms important in tumor-induced angiogenesis in human breast cancer.