Department of Ultrasound, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, 230036, Anhui, People's Republic of China.
Department of Ultrasound, Xinhua Hospital Affiliated to Shanghai Jiaotong University, 200092, Shanghai, People's Republic of China.
BMC Cancer. 2022 Feb 16;22(1):173. doi: 10.1186/s12885-022-09266-0.
Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge.
Under the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described.
The DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n = 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma.
This study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.
原位 LNCaP 异种移植小鼠模型密切模拟人类雄激素依赖性前列腺癌的进展；然而，将 LNCaP 细胞原位注射到小鼠前列腺仍然具有挑战性。
在立体显微镜的引导下，研究了雄性 Balb/c 无胸腺裸鼠前列腺各叶的解剖结构，并将 LNCaP 细胞接种到小鼠背侧前列腺（DP）中，以生成模拟人类前列腺癌病理生理过程的原位肿瘤。实时超声成像用于监测原位前列腺肿瘤发生，对比增强超声（CEUS）用于表征肿瘤血管生成，描述肿瘤的宏观和微观特征。
DP 呈三角双锥形，位于精囊底部。原位接种后，灰阶超声成像显示肿瘤回声纹理、形状和位置的进行性变化，肿瘤倾向于向膀胱突出。8 周后，肿瘤接种率为 65%（n=20 只小鼠中的 13 只）。在 CEUS 上，信号强度迅速增加，达到峰值，然后逐渐下降。大体标本观察显示，原位前列腺肿瘤边界清楚，呈圆形，深褐色，质地柔软，外表面光滑，有光泽。显微镜下，肿瘤细胞排列在被纤维隔包围的腺泡中，壁厚度不等，类似于人类腺癌。
本研究描述了一种成功建立原位 LNCaP 异种移植 Balb/c 无胸腺裸鼠模型的方法。该模型需要深入了解小鼠前列腺解剖结构和正确的技术。该模型代表了一种有价值的工具，可用于研究前列腺癌中血管生成涉及的生物学过程，并对新型抗血管生成治疗进行临床前评估。
