Princess Margaret Cancer Centre, Toronto, Canada.
Department of Radiation Oncology, University of Toronto, Toronto, Canada.
Prostate. 2024 Jun;84(9):823-831. doi: 10.1002/pros.24701. Epub 2024 Apr 12.
There are limited preclinical orthotopic prostate cancer models due to the technical complexity of surgical engraftment and tracking the tumor growth in the mouse prostate gland. Orthotopic xenografts recapitulate the tumor microenvironment, tumor stromal interactions, and clinical behavior to a greater extent than xenografts grown at subcutaneous or intramuscular sites.
This study describes a novel micro-surgical technique for orthotopically implanting intact tumors pieces from cell line derived (transgenic adenocarcinoma mouse prostate [TRAMP]-C2) or patient derived (neuroendocrine prostate cancer [NEPC]) tumors in the mouse prostate gland and monitoring tumor growth using magnetic resonance (MR) imaging.
The TRAMP-C2 tumors grew rapidly to a predetermined endpoint size of 10 mm within 3 weeks, whereas the NEPC tumors grew at a slower rate over 7 weeks. The tumors were readily detected by MR and confidently identified when they were approximately 2-3 mm in size. The tumors were less well-defined on CT. The TRAMP-C2 tumors were characterized by amorphous sheets of poorly differentiated cells similar to a high-grade prostatic adenocarcinoma and frequent macroscopic peritoneal and lymph node metastases. In contrast, the NEPC's displayed a neuroendocrine morphology with polygonal cells arranged in nests and solid sheets and high count. There was a local invasion of the bladder and other adjacent tissues but no identifiable metastases. The TRAMP-C2 tumors were more hypoxic than the NEPC tumors.
This novel preclinical orthotopic prostate cancer mouse model is suitable for either syngeneic or patient derived tumors and will be effective in developing and advancing the current selection of treatments for patients with prostate cancer.
由于手术植入的技术复杂性以及在小鼠前列腺中跟踪肿瘤生长，临床上可应用的前列腺癌原位模型有限。与在皮下或肌肉内生长的异种移植物相比，原位异种移植物在更大程度上再现了肿瘤微环境、肿瘤基质相互作用和临床行为。
本研究描述了一种新的微外科技术，用于将源自细胞系（转基因腺癌小鼠前列腺[TRAMP]-C2）或源自患者（神经内分泌前列腺癌[NEPC]）的完整肿瘤块原位植入小鼠前列腺，并使用磁共振（MR）成像监测肿瘤生长。
TRAMP-C2 肿瘤在 3 周内迅速生长到预定的 10mm 终点大小，而 NEPC 肿瘤则在 7 周内以较慢的速度生长。MR 可轻松检测到肿瘤，当肿瘤大小约为 2-3mm 时，可准确识别肿瘤。CT 上肿瘤显示较差。TRAMP-C2 肿瘤的特征是形态不规则的低分化细胞片，类似于高级别前列腺腺癌，并且经常出现宏观腹膜和淋巴结转移。相比之下，NEPC 显示出神经内分泌形态，多边形细胞排列成巢状和实性片状，计数较高。膀胱和其他相邻组织有局部浸润，但无可识别的转移。TRAMP-C2 肿瘤比 NEPC 肿瘤更缺氧。
这种新型临床前前列腺癌原位小鼠模型适合用于同种异体或患者来源的肿瘤，将有效地开发和推进当前针对前列腺癌患者的治疗选择。
