Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach.
Ultrasound-guided intramural inoculation of orthotopic bladder cancer xenografts: a novel high-precision approach.
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DOI：
10.1371/journal.pone.0059536
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Black PC
中科院分区：
文献类型：
--
作者：
Jäger W;Moskalev I;Janssen C;Hayashi T;Awrey S;Gust KM;So AI;Zhang K;Fazli L;Li E;Thüroff JW;Lange D;Black PC
原位膀胱癌异种移植物对于测试体内细胞系的新疗法和分子操作是必不可少的。目前的异种移植依赖于通过膀胱内滴注或直接注射到膀胱壁中的肿瘤细胞接种。滴注受到以这种方式输送时缺乏致瘤细胞系的限制。侵入性模型由于需要剖腹手术和膀胱移动而使小鼠发病。此外，这一程序既复杂又耗时。将3株膀胱癌细胞系（UM-UC 1、UM-UC 3、UM-UC 13）在超声引导下经皮接种于50只裸鼠体内。首先在肌肉壁和粘膜之间注射PBS以分离这些层，随后将肿瘤细胞注射到该空间中。使用生物发光和超声来监测肿瘤生长。超声造影用于研究全身吉西他滨/顺铂治疗后肿瘤灌注的变化。为了证明可以在超声引导下将治疗剂注射到建立的异种移植物中的原理证据，将溶瘤病毒（VSV）注射到UM-UC 3肿瘤中。23-37天后收获异种移植组织用于免疫组织化学。在所有50只动物中，经皮将肿瘤细胞注射到膀胱壁中是有效的（平均时间：5.7分钟），并且没有并发症。3天后，超声和生物发光证实所有动物的膀胱前壁均存在肿瘤。平均肿瘤体积在研究期间稳步增加。UM-UC 13肿瘤化疗后体积和灌注明显减少。VSV-G的免疫组织化学染色证实了瘤内注射后所有UM-UC 3肿瘤中的病毒摄取。我们已经开发出一种新的方法，以微创的方式建立原位膀胱癌异种移植。在我们手中，这已经取代了需要剖腹手术的传统模型，因为这种模型更省时，更精确，并且与小鼠的发病率更低相关。
Orthotopic bladder cancer xenografts are essential for testing novel therapies and molecular manipulations of cell lines in vivo. Current xenografts rely on tumor cell inoculation by intravesical instillation or direct injection into the bladder wall. Instillation is limited by the lack of cell lines that are tumorigenic when delivered in this manner. The invasive model inflicts morbidity on the mice by the need for laparotomy and mobilization of the bladder. Furthermore this procedure is complex and time-consuming. Three bladder cancer cell lines (UM-UC1, UM-UC3, UM-UC13) were inoculated into 50 athymic nude mice by percutaneous injection under ultrasound guidance. PBS was first injected between the muscle wall and the mucosa to separate these layers, and tumor cells were subsequently injected into this space. Bioluminescence and ultrasound were used to monitor tumor growth. Contrast-enhanced ultrasound was used to study changes in tumor perfusion after systemic gemcitabine/cisplatin treatment. To demonstrate proof of principle that therapeutic agents can be injected into established xenografts under ultrasound guidance, oncolytic virus (VSV) was injected into UM-UC3 tumors. Xenograft tissue was harvested for immunohistochemistry after 23–37 days. Percutaneous injection of tumor cells into the bladder wall was performed efficiently (mean time: 5.7 min) and without complications in all 50 animals. Ultrasound and bioluminescence confirmed presence of tumor in the anterior bladder wall in all animals 3 days later. The average tumor volumes increased steadily over the study period. UM-UC13 tumors showed a marked decrease in volume and perfusion after chemotherapy. Immunohistochemical staining for VSV-G demonstrated virus uptake in all UM-UC3 tumors after intratumoral injection. We have developed a novel method for creating orthotopic bladder cancer xenograft in a minimally invasive fashion. In our hands this has replaced the traditional model requiring laparotomy, because this model is more time efficient, more precise and associated with less morbidity for the mice.
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