Choi Jin Woo, Cho Hye Rim, Lee Kyoungbun, Jung Jae Kyung, Kim Hyo-Cheol
Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
J Vasc Interv Radiol. 2018 Nov;29(11):1604-1612. doi: 10.1016/j.jvir.2018.07.005. Epub 2018 Oct 5.
To compare tumor vascularity in 4 types of rat hepatocellular carcinoma (HCC) models: N1S1, vascular endothelial growth factor (VEGF)-transfected N1S1 (VEGF-N1S1), McA-RH7777, and VEGF-transfected McA-RH7777 (VEGF-McA-RH777) tumors.
The N1S1 and McA-RH7777 cell lines were transfected with expression vectors containing cDNA for rat VEGF. Eighty-eight male Sprague-Dawley rats (weight range, 400-450 g) were randomly divided into 4 groups (ie, 22 rats per model), and 4 types of tumor models were created by using the N1S1, VEGF-N1S1, McA-RH7777, and VEGF-McA-RH777 cell lines. Tumor vascularity was evaluated by perfusion computed tomography (CT), enzyme-linked immunosorbent assay of VEGF, CD34 staining, angiography, and Lipiodol transarterial embolization. Intergroup discrepancies were evaluated by Kruskal-Wallis test.
Arterial perfusion (P < .001), portal perfusion (P = .015), total perfusion (P < .001), tumor VEGF level (P = .002), and microvessel density (MVD; P = .007) were significantly different among groups. VEGF-McA-RH7777 tumors showed the greatest arterial perfusion (46.7 mL/min/100 mL ± 15.5), total perfusion (60.7 mL/min/100 mL ± 21.8), tumor VEGF level (3,376.7 pg/mL ± 145.8), and MVD (34.5‰ ± 7.5). Whereas most tumors in the N1S1, VEGF-N1S1, and McA-RH7777 groups showed hypovascular staining on angiography and minimal Lipiodol uptake after embolization, 5 of 6 VEGF-McA-RH7777 tumors (83.3%) presented hypervascular tumor staining and moderate to compact Lipiodol uptake.
McA-RH7777 tumors were more hypervascular than N1S1 tumors, and tumor vascularity was enhanced further by VEGF transfection. Therefore, the VEGF-McA-RH7777 tumor is recommended to mimic hypervascular human HCC in rats.
比较4种大鼠肝细胞癌（HCC）模型中的肿瘤血管生成情况，这4种模型分别为：N1S1、血管内皮生长因子（VEGF）转染的N1S1（VEGF-N1S1）、McA-RH7777以及VEGF转染的McA-RH7777（VEGF-McA-RH777）肿瘤模型。
将含有大鼠VEGF cDNA的表达载体转染至N1S1和McA-RH7777细胞系。88只雄性Sprague-Dawley大鼠（体重范围400 - 450 g）随机分为4组（即每种模型22只大鼠），使用N1S1、VEGF-N1S1、McA-RH7777和VEGF-McA-RH777细胞系建立4种肿瘤模型。通过灌注计算机断层扫描（CT）、VEGF酶联免疫吸附测定、CD34染色、血管造影以及碘油经动脉栓塞术评估肿瘤血管生成情况。采用Kruskal-Wallis检验评估组间差异。
各组间动脉灌注（P <.001）、门静脉灌注（P =.015）、总灌注（P <.001）、肿瘤VEGF水平（P =.002）和微血管密度（MVD；P =.007）存在显著差异。VEGF-McA-RH7777肿瘤模型显示出最大的动脉灌注（46.7 mL/min/100 mL ± 15.5）、总灌注（60.7 mL/min/100 mL ± 21.8）、肿瘤VEGF水平（3376.7 pg/mL ± 145.8）和MVD（34.5‰ ± 7.5）。在血管造影中，N1S1、VEGF-N1S1和McA-RH7777组的大多数肿瘤显示为低血运染色，栓塞后碘油摄取极少，而VEGF-McA-RH7777组的6个肿瘤中有5个（83.3%）呈现高血运肿瘤染色以及中度至致密的碘油摄取。
McA-RH7777肿瘤比N1S1肿瘤血运更丰富，VEGF转染进一步增强了肿瘤血管生成。因此，推荐使用VEGF-McA-RH7777肿瘤模型在大鼠中模拟人类高血运HCC。
