In vivo assessment of RAS-dependent maintenance of tumor angiogenesis by real-time magnetic resonance imaging
In vivo assessment of RAS-dependent maintenance of tumor angiogenesis by real-time magnetic resonance imaging
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DOI：
10.1158/0008-5472.can-05-0027
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发表时间：
2005-09-15
期刊：
影响因子：
11.2
通讯作者：
Weissleder, R
中科院分区：
文献类型：
--
作者：
Tang, Y;Kim, M;Weissleder, R
新血管形成是人类癌症和肿瘤进展的突出特征，并且经常伴随着与促血管生成和抗血管生成分子平衡中的转换相关的血管生成表型的获得。本研究旨在使用体内成像与组织病理学相关性研究激活的H-RAS对诱导型Tyr/Tet-RAS Ink 4a/Arf（-/-）模型中出现的黑色素瘤血管生成表型的作用。我们发现，RAS活性的损失在完全建立的黑色素瘤导致肿瘤体积的减少，这是由体内磁共振成像确定的血管功能受损之前。这与宿主来源的内皮细胞以及肿瘤细胞中的凋亡活化相关。因此，实时体内成像提供的证据表明，肿瘤血管生成的维持需要该模型系统中激活的RAS，并且RAS失活后血管完整性的丧失是一个主动过程，而不是肿瘤细胞活力丧失的结果。
New blood vessel formation is a prominent feature of human cancers and tumor progression and is frequently accompanied by the acquisition of an angiogenic phenotype associated with a switch in the balance of proangiogenic and antiangiogenic molecules. This study was designed to investigate the role of activated H-RAS on the angiogenic phenotype of melanoma that arises in the inducible Tyr/Tet-RAS Ink4a/Arf(-/-) model using in vivo imaging with histopathologic correlation. We show that loss of RAS activity in fully established melanomas led to a reduction in tumor volume, which was preceded by impairment of vascular function as determined by in vivo magnetic resonance imaging. This correlated with activation of apoptosis in host-derived endothelial cells as well as in tumor cells. Thus, real-time in vivo imaging provided evidence that maintenance of tumor angiogenesis requires activated RAS in this model system, and that loss of vascular integrity upon inactivation of RAS is an active process rather than a consequence of loss of tumor cell viability.