Pavese Janet, Ogden Irene M, Bergan Raymond C
Department of Medicine, Northwestern University.
J Vis Exp. 2013 Sep 18(79):e50873. doi: 10.3791/50873.
Our laboratory has developed a novel orthotopic implantation model of human prostate cancer (PCa). As PCa death is not due to the primary tumor, but rather the formation of distinct metastasis, the ability to effectively model this progression pre-clinically is of high value. In this model, cells are directly implanted into the ventral lobe of the prostate in Balb/c athymic mice, and allowed to progress for 4-6 weeks. At experiment termination, several distinct endpoints can be measured, such as size and molecular characterization of the primary tumor, the presence and quantification of circulating tumor cells in the blood and bone marrow, and formation of metastasis to the lung. In addition to a variety of endpoints, this model provides a picture of a cells ability to invade and escape the primary organ, enter and survive in the circulatory system, and implant and grow in a secondary site. This model has been used effectively to measure metastatic response to both changes in protein expression as well as to response to small molecule therapeutics, in a short turnaround time.
我们实验室开发了一种新型的人前列腺癌(PCa)原位植入模型。由于前列腺癌导致的死亡并非源于原发性肿瘤,而是源于不同转移灶的形成,因此在临床前有效模拟这种进展的能力具有很高的价值。在该模型中,将细胞直接植入Balb/c裸鼠的前列腺腹叶,并使其进展4至6周。在实验结束时,可以测量几个不同的终点指标,例如原发性肿瘤的大小和分子特征、血液和骨髓中循环肿瘤细胞的存在及定量,以及肺转移的形成。除了各种终点指标外,该模型还展示了细胞侵入和逃离原发器官、进入循环系统并在其中存活,以及在继发部位植入和生长的能力。该模型已被有效地用于在短时间内测量对蛋白质表达变化的转移反应以及对小分子疗法的反应。