Peiffer Lauren B, Hicks Jessica, Sosa Rebecca Y, De Marzo Angelo M, Sfanos Karen S, Maynard Janielle P
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Front Oncol. 2022 Apr 27;12:877536. doi: 10.3389/fonc.2022.877536. eCollection 2022.
The 5-year survival rate for patients diagnosed with distant metastatic prostate cancer in the United States is 30.6%. Therefore, there is a great need to develop model systems to study prostate cancer metastasis and to test potential therapeutics. Most murine prostate cancer metastatic models involve intracardiac or intraosseous implantation of cancer cells, which bypass the early stages of tumor cell migration and invasion. Herein we provide a detailed protocol for a novel method of resecting subcutaneous prostate cancer allografts in immunocompetent mice to produce spontaneous metastases and describe a pilot study using this method of tumor resection. Intact male FVB/NCrl mice (n = 9) were inoculated subcutaneously with Myc-CaP cells. Tumors were surgically resected, and mice were monitored for tumor recurrence. Animals were euthanized or died, and a full set of tissues was collected for histopathologic examination. Tumors took an average of 44 days (range 23-61) to reach 1.7 cm in any direction. All tumors were resectable, and resection of the tumors increased the study length by 70 days (range 30-121). One mouse was euthanized early of an unrelated cause, and of eight remaining mice, four developed tumor recurrence at the site of resection. One mouse developed bone metastases, one mouse developed metastases to the abdominal cavity, and two mice showed signs of local invasion. This study demonstrates that resection of subcutaneous Myc-CaP cell allografts in mice results in local tumor recurrence and the development of distant metastases, providing a new model system to study prostate cancer metastasis .
在美国，被诊断为远处转移性前列腺癌的患者5年生存率为30.6%。因此，迫切需要开发模型系统来研究前列腺癌转移并测试潜在的治疗方法。大多数小鼠前列腺癌转移模型涉及癌细胞的心内或骨内植入，这绕过了肿瘤细胞迁移和侵袭的早期阶段。在此，我们提供了一种详细的方案，用于在具有免疫活性的小鼠中切除皮下前列腺癌同种异体移植物以产生自发转移的新方法，并描述了一项使用这种肿瘤切除方法的初步研究。将完整的雄性FVB/NCrl小鼠（n = 9）皮下接种Myc-CaP细胞。手术切除肿瘤，并监测小鼠的肿瘤复发情况。对动物实施安乐死或动物死亡后，收集全套组织进行组织病理学检查。肿瘤在任何方向达到1.7厘米平均需要44天（范围23 - 61天）。所有肿瘤均可切除，肿瘤切除使研究时长增加了70天（范围30 - 121天）。一只小鼠因无关原因提前实施安乐死，在其余8只小鼠中，4只在切除部位出现肿瘤复发。1只小鼠发生骨转移，1只小鼠发生腹腔转移，2只小鼠出现局部侵袭迹象。本研究表明，切除小鼠皮下Myc-CaP细胞同种异体移植物会导致局部肿瘤复发和远处转移的发生，为研究前列腺癌转移提供了一个新的模型系统。
