RENCA/carbonic anhydrase-IX: a murine model of a carbonic anhydrase-IX-expressing renal cell carcinoma.

Autor: Shvarts O; Department of Urology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-1738, USA., Janzen N, Lam JS, Leppert JT, Caliliw R, Figlin RA, Belldegrun AS, Zeng G
Jazyk: angličtina
Zdroj: Urology [Urology] 2006 Nov; Vol. 68 (5), pp. 1132-8. Date of Electronic Publication: 2006 Nov 07.
DOI: 10.1016/j.urology.2006.08.1073
Abstrakt: Objectives: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Databáze: MEDLINE
Externí odkaz: