Fliedner Frederikke P, Hansen Anders E, Jørgensen Jesper T, Kjær Andreas
Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Department of Micro- and Nanotechnology, Center for Nanomedicine and Theranostics, DTU Nanotech, Technical University of Denmark, Building 423, 2800, Lyngby, Denmark.
BMC Med Imaging. 2016 Jan 14;16:5. doi: 10.1186/s12880-016-0105-4.
In preclinical research Matrixgel(TM) Basement Membrane Matrix (MG) is used frequently for the establishment of syngeneic and xenograft cancer models. Limited information on its influence on parameters including; tumor growth, vascularization, hypoxia and imaging characteristics is currently available. This study evaluates the potential effect of matrigel use in a human head and neck cancer xenograft model (FaDu; hypopharyngeal carcinoma) in NMRI nude mice. The FaDu cell line was chosen based on its frequent use in studies of cancer imaging and tumor microenvironment.
NMRI nude mice (n = 34) were divided into two groups and subcutaneously injected with FaDu cells in medium either including (+MG) or excluding matrigel (-MG). In sub study I seven mice from each group (+MG, n = 7; -MG, n = 7) were (18)F- fluorodeoxyglucose ((18)F-FDG) PET/CT scanned on Day 5, 8, 12, 15, and 19. In sub study II ten mice from each group (+MG, n = 10; -MG, n = 10) were included and tumors collected for immunohistochemistry (IHC) analysis of tumor microenvironment including; proliferation ratio, micro vessel density, average vessel area, hypoxia, nuclear density, and necrosis. Tumors for IHC were collected according to size (200-400 mm(3), 500-700 mm(3), 800-1100 mm(3)).
FDG uptake and tumor growth was statistically compatible for the tumors established with or without MG. The IHC analysis on all parameters only identified a significantly higher micro vessel density for tumor size 500-700 mm(3) and 800-1100 mm(3) and average vessel area for tumor size 500-700 mm(3) in the -MG group. Comparable variations were observed for tumors of both the +MG and -MG groups. No difference in tumor take rate was observed between groups in study.
Matrigel did not affect tumor growth or tumor take for the FaDu xenograft model evaluated. Tumors in the -MG group displayed increased angiogenesis compared to the +MG tumors. No difference in (18)F-FDG PET uptake for tumors of different groups was found. Based on these observations the influence of matrigel on tumor imaging and tumor microenvironment seems minor for this particular xenograft model.
在临床前研究中,基质胶(Matrixgel™)基底膜基质(MG)经常用于建立同基因和异种移植癌症模型。目前关于其对包括肿瘤生长、血管生成、缺氧和成像特征等参数影响的信息有限。本研究评估了在NMRI裸鼠的人头颈癌异种移植模型(FaDu;下咽癌)中使用基质胶的潜在影响。选择FaDu细胞系是基于其在癌症成像和肿瘤微环境研究中的频繁使用。
将NMRI裸鼠(n = 34)分为两组,分别皮下注射含(+MG)或不含基质胶(-MG)的培养基中的FaDu细胞。在子研究I中,每组7只小鼠(+MG,n = 7;-MG,n = 7)在第5、8、12、15和19天进行(18)F-氟脱氧葡萄糖((18)F-FDG)PET/CT扫描。在子研究II中,每组纳入10只小鼠(+MG,n = 10;-MG,n = 10),收集肿瘤用于肿瘤微环境的免疫组织化学(IHC)分析,包括增殖率、微血管密度、平均血管面积、缺氧、核密度和坏死。根据大小(200 - 400 mm³、500 - 700 mm³、800 - 1100 mm³)收集用于IHC的肿瘤。
对于有或无MG建立的肿瘤,FDG摄取和肿瘤生长在统计学上具有可比性。对所有参数的IHC分析仅发现,在-MG组中,肿瘤大小为500 - 700 mm³和800 - 1100 mm³时微血管密度显著更高,肿瘤大小为500 - 700 mm³时平均血管面积显著更高。+MG组和-MG组的肿瘤均观察到类似变化。研究中两组之间未观察到肿瘤接种率的差异。
对于所评估的FaDu异种移植模型,基质胶不影响肿瘤生长或肿瘤接种。与+MG肿瘤相比,-MG组的肿瘤显示出血管生成增加。不同组肿瘤的(18)F-FDG PET摄取未发现差异。基于这些观察结果,对于这个特定的异种移植模型,基质胶对肿瘤成像和肿瘤微环境的影响似乎较小。