Isolation and characterization of an immortalized mouse urogenital sinus mesenchyme cell line

BACKGROUND. Stromal-epithelial signaling plays an important role in prostate development and cancer progression. Study of these interactions will be facilitated by the use of suitable prostate cell lines in appropriate model systems. METHODS. We have isolated an immortalized prostate mesenchymal cell line from the mouse E16 urogenital sinus (UGS). We characterized its expression of stromal differentiation markers, response to androgen stimulation, ability to induce and participate in prostate morphogenesis, response to Shh stimulation, and interaction with prostate epithelial cells. RESULTS. UGSM-2 cells express vimentin and smooth muscle actin, but not the mature smooth muscle markers myosin and desmin. This expression profile is consistent with a myofibroblast phenotype. Unlike other fibroblasts such as 3T3, UGSM-2 cells express androgen receptor mRNA and androgen stimulation increases proliferation. UGSM-2 cells are viable when grafted with embryonic UGS under the renal capsule and participate in glandular morphogenesis, but are not capable of inducing prostate morphogenesis of isolated UGS epithelium. Co-culture of UGSM-2 cells with human BPH-1 cells or co-grafting in vivo results in organized clusters of BPH-1 cells surrounded by a mantle of UGSM-2 cells. UGSM-2 cells are responsive to Sonic hedgehog (Shh), an important signaling factor in prostate development, and mimic the transcriptional response of the intact UGS mesenchyme. In co-cultures with BPH-1, UGSM-2 cells exhibit a robust transcriptional response to Shh secreted by BPH-1. CONCLUSIONS. UGSM-2 is a urogenital sinus mesenchyme cell line that can be used to study stromal-epithelial interactions that are important in prostate biology.