Transplantation of human breast epithelia to mammary-gland-free fat-pads of athymic nude mice: influence of mammotrophic hormones on growth of breast epithelia

Abstract

Normal human breast tissue was enzymatically dissociated and the cells were injected into the gland-free fat-pads of athymic nude mice. Within 30 days, small, spherical, duct-like epithelial elements (organoids) formed in 68% of the fat-pads inoculated (0-23 organoids/fat-pad). Short-term (30-day) treatment of the host mice with mammotrophic hormones [secretions from a chorionic, soamto-mammotrophin-secreting transplantable human choriocarcinoma (JEG-3), secretions from a prolactin- and growth-hormone-secreting transplantable rat pituitary tumor (GH3), estrogen and/or progesterone] and/or cAMP inducers (cholera toxin) significantly (p less than 0.05) increased the size of the human breast organoids but did not increase organoid number or induce extensive and expansive growth (extensive duct elongation and branching) of these structures. Such treatments induced intense proliferation of the host mouse mammae resembling that which occurs during late pregnancy. The results of this study, therefore, provide evidence that normal human breast epithelium can be readily accepted by and maintained in the gland-free fat-pad of the athymic nude mouse, and the epithelium, within 30 days, forms spherical duct-like structures (organoids). The human breast organoids are hormone-responsive, as they respond to a mammotrophic growth stimulus by an increase in size. The failure of the human breast organoids to grow expansively in the gland-free fat-pad of this immunologically deficient mouse does not appear to be due to the absence of an appropriate hormonal growth stimulus.