RENCA/carbonic anhydrase-IX: a murine model of a carbonic anhydrase-IX-expressing renal cell carcinoma.
OBJECTIVE
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.
Shvarts
Oleg
O
Department of Urology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, California 90095-1738, USA.
Janzen
Nicolette
N
Lam
John S
JS
Leppert
John T
JT
Caliliw
Randy
R
Figlin
Robert A
RA
Belldegrun
Arie S
AS
Zeng
Gang
G
D000818:Animals; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D007680:Kidney Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C
D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; C492796:Car9 protein, mouse