Differential Expression of the α2 Chain of the Interleukin-13 Receptor in Metastatic Human Prostate Cancer ARCaPM Cells.

BACKGROUND. The alpha 2 chain of the interleukin-13 receptor (IL13R alpha 2) is a high-affinity receptor and a candidate target for cytotoxic killing of cancer cells. Availability of a human prostate cancer cell line with high level of IL13R alpha 2 expression will facilitate the development of therapeutic modalities. METHODS. ARCaP(E) and ARCaP(M) human prostate cancer cell lines were subjected to comparative analyses of gene expression. Expression of the IL13R alpha 2 protein was confirmed by Western blotting and immunostaining. IL13R alpha 2 proteihs in xenograft tumors and clinical human prostate cancer specimens were detected by specific antibodies. LNCaP prostate cancer cells stably transfected with IL13R alpha 2 were examined for accelerated growth in athymic mice. RESULTS. We found that IL13R alpha 2 proteins could be detected in both the ARCaP(E) and ARCaP(M) cells, but the expression level in ARCaP(M) was more than 17-fold higher than in ARCaP(E) cells. Importantly, the ARCaP lineage represented the only human prostate cancer cell line that expresses IL13R alpha 2 proteins at the level detectable by Western blotting. Expression of IL13R alpha 2 was accompanied by resistance to the anti-tumor activity of interleukin-13 (IL-13). ARCaP cells were found to be insensitive to growth inhibition upon IL-13 treatment, while overexpression of IL13R alpha 2 in LNCaP cells promoted intratibial tumor growth in athymic mice. CONCLUSIONS. Differential IL13R alpha 2 expression may account for the high tumorigenic and metastatic potential of ARCaP(M) cells. The unique expression of IL13R alpha 2 makes ARCaP lineage an attractive model for evaluating the targeting efficacy of therapeutic agents based on IL13R alpha 2 protein expression. Prostate 70: 993-1001, 2010. (c) 2010 Wiley-Liss, Inc.