Shvarts Oleg, Janzen Nicolette, Lam John S, Leppert John T, Caliliw Randy, Figlin Robert A, Belldegrun Arie S, Zeng Gang
Department of Urology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-1738, USA.
Urology. 2006 Nov;68(5):1132-8. doi: 10.1016/j.urology.2006.08.1073. Epub 2006 Nov 7.
Carbonic anhydrase-IX (CA-IX) is a cell surface tumor-associated antigen expressed by most clear cell renal cell carcinomas (RCCs). The specificity and the prognostic value of CA-IX provide impetus to create a mouse model of CA-IX-expressing RCC for testing CA-IX-targeted therapies against RCC.
A retrovirus encoding the human CA-IX gene was used to transduce the murine RCC line, RENCA. In vivo growth kinetics and CA-IX expression were compared between RENCA and RENCA/CA-IX using heterotopic, metastatic, and orthotopic models.
Transduction of RENCA created the RENCA/CA-IX line with nearly 100% CA-IX surface expression. In the heterotopic model, subcutaneous injection of 500,000 and 50,000 cells led to tumor formation at 2 to 2.5 weeks after injection, with similar growth kinetics between the two cell lines at either cell number. In the pulmonary metastatic model, a similar number of metastases was noted after inoculation of RENCA and RENCA/CA-IX. In the orthotopic model, autopsy revealed a CA-IX-expressing renal tumor, as well as CA-IX-expressing metastases to the lungs, liver, contralateral kidney, intestines, and lymph nodes. In all the above models, the RENCA/CA-IX tumors retained expression of CA-IX, as demonstrated by immunohistochemistry staining.
RENCA/CA-IX is the first tumor model that manifests in immunocompetent Balb/c mice and stably expresses a defined kidney cancer-associated antigen. It maintains antigen expression, forms metastases, and produces reliable tumor growth kinetics equivalent to that of its parental cell line.
碳酸酐酶-IX（CA-IX）是一种细胞表面肿瘤相关抗原，大多数透明细胞肾细胞癌（RCC）均有表达。CA-IX的特异性和预后价值推动了构建表达CA-IX的RCC小鼠模型，以测试针对RCC的CA-IX靶向治疗。
使用编码人CA-IX基因的逆转录病毒转导小鼠RCC细胞系RENCA。使用异位、转移和原位模型比较RENCA和RENCA/CA-IX的体内生长动力学和CA-IX表达。
RENCA的转导产生了RENCA/CA-IX细胞系，其CA-IX表面表达率接近100%。在异位模型中，皮下注射500,000和50,000个细胞后，在注射后2至2.5周形成肿瘤，两种细胞系在任一细胞数量下的生长动力学相似。在肺转移模型中，接种RENCA和RENCA/CA-IX后观察到的转移灶数量相似。在原位模型中，尸检发现一个表达CA-IX的肾肿瘤，以及肺、肝、对侧肾、肠和淋巴结的CA-IX转移灶。在上述所有模型中，免疫组织化学染色显示RENCA/CA-IX肿瘤保留了CA-IX的表达。
RENCA/CA-IX是第一个在免疫健全的Balb/c小鼠中表现并稳定表达特定肾癌相关抗原的肿瘤模型。它维持抗原表达，形成转移灶，并产生与其亲本细胞系相当的可靠肿瘤生长动力学。
