Transplanted mammary epithelium grows in association with host stroma: aging of serially transplanted mammary gland is intrinsic to epithelial cells.

Mouse mammary gland displays an irreversible decline in growth rate when propagated by serial transplantation in gland-free mammary fat pads of isogeneic mice. Because transplanted fragments of gland contain both mammary epithelial and stromal elements, the present study was undertaken to distinguish between two possibilities: (1) stromal cells in the implants proliferate in coordination with epithelium as the mammary ductal tree regenerates at each passage, or (2) transplanted epithelial tissue interacts exclusively with host stroma. Mammary xenografts from 18-week-old virgin Sprague-Dawley rats were implanted into gland-free mammary fat pads of athymic Balb/cNu/Nu mice. These rat xenografts regenerated chimeric mammary ductal outgrowths. When sectioned and stained with Hoechst dye 33258, a procedure that provides for unambiguous identification of mouse cell nuclei, rat mammary epithelium was found to be associated with mouse stromal cells; only at the site of transplantation were occasional rat stromal nuclei observed. This indicates that as mouse epithelial tissue becomes progressively aged during serial transfer in young mice, the stromal components are refreshed during each passage. The primary lesion underlying the mammary aging phenomenon must therefore be intrinsic to the epithelial cells.