Shan Siqing, Sorg Brian, Dewhirst Mark W
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Microvasc Res. 2003 Mar;65(2):109-17. doi: 10.1016/s0026-2862(02)00017-1.
Orthotopic and ectopic organ environments differentially influence tumor growth, metastasis, and sensitivity to therapy. In this study we present a novel rodent mammary window of orthotopic breast cancer, which is amenable to study of microvascular function and angiogenesis in this orthotopic site. The skin around the nipple of selected mammary glands of female Fischer 344 rats was removed and the nipple was cut at its base. R3230Ac tumor fragments or cells in Gelfoam were aseptically implanted into the nipple sinus. An acrylic disk was placed on top of the implant and was sutured in place. Histology showed that tumors were well established within 5 days. Similar techniques were also applied to BALB/c mice transplanted with 4T1 murine mammary carcinoma cells. With GFP-expressing tumor cells and serial observations, we demonstrated unique patterns of tumor cell proliferation and vascularization in both tumor models. The images obtained were comparable to those from the dorsal skinfold window chambers. This model will allow for study of tumor microcirculatory function, angiogenesis, tumor cell-host interactions, and evaluation of effects of various treatments.
原位和异位器官环境对肿瘤生长、转移及治疗敏感性有不同影响。在本研究中,我们展示了一种新型的原位乳腺癌啮齿动物乳腺窗口模型,该模型适用于研究此原位部位的微血管功能和血管生成。切除雌性Fischer 344大鼠选定乳腺乳头周围的皮肤,并在乳头基部将其切断。将R3230Ac肿瘤碎片或置于明胶海绵中的细胞无菌植入乳头窦。在植入物上方放置一个丙烯酸盘并缝合固定。组织学显示肿瘤在5天内即可良好形成。类似技术也应用于移植了4T1小鼠乳腺癌细胞的BALB/c小鼠。通过表达绿色荧光蛋白的肿瘤细胞和连续观察,我们在两种肿瘤模型中都证明了肿瘤细胞增殖和血管化的独特模式。所获得的图像与背部皮肤褶皱窗口小室的图像相当。该模型将有助于研究肿瘤微循环功能、血管生成、肿瘤细胞与宿主的相互作用,以及评估各种治疗的效果。