3851

BALB-Rag2-/-;γc-/- mice, developed by the Central Institute for Experimental Animals (CIEA, Kawasaki, Japan), lack the expression of both the recombinase activating gene 2 (Rag2) and the common cytokine receptor γ chain (γc) and show a complete absence of T, B and NK responses. These mice should accept xenotransplants of both immune and nonimmune cells much better than other immunodeprived mice such as nude or SCID mice, which retain NK activity.

We took advantage of BALB-Rag2-/-;γc-/- mice to investigate the metastatic potential of several human tumor cell lines of different histotypes (rhabdomyosarcoma, Ewing’s sarcoma, osteosarcoma, breast and colorectal carcinoma cell lines). Metastases were induced by intravenous cell injection. The different cell lines showed unique metastatic patterns. Most human tumor cell lines were able to metastasize to lungs, but strongly differed in metastases incidence and number. Liver metastasization was even more specific: most sarcoma cell lines gave rise to multiple huge liver metastatic lesions, in some cases in the absence of lung metastases. Parallel experiments in nude mice with NK depletion (through anti-asialo treatment) failed to show liver metastases. Therefore BALB-Rag2-/-;γc-/- mice can be a highly effective model to study liver metastases of human tumor cells, and could allow to evaluate new therapeutic treatments.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA