Anti-metastatic outcome of isoform-specific prolactin receptor targeting in breast cancer

摘要: Controversy exists concerning the role of long prolactin receptor (PRLR) in progression breast cancer. By targeting pre-mRNA splicing, we succeeded knocking down only PRLR vivo, leaving short forms unaffected. Using two orthotopic and highly-metastatic models cancer, one which was syngeneic (mouse 4T1) to allow assessment tumor-immune interactions endocrinologically humanized (human BT-474) activate human PRLRs, examined effect knockdown on disease progression. In both models, dramatically inhibited metastatic spread lungs liver resulted increased central death primary tumor. model, immune infiltrates sites were changed from innate inflammatory cells lymphocytes, with an increase incidence tumor-specific cytotoxic T cells. Long three-dimensional culture induced apoptosis tumor-initiating/cancer stem (death 95% displaying cell markers 15 days). We conclude that plays important cancer metastasis.