Abstract B56: Prolactin promotes breast cancer to bone metastasis and breast cancer cell-mediated osteoclast differentiation

The hormones prolactin (PRL), estrogen and progesterone have long been studied for their role in the primary breast tumor but not yet in modulating the secondary tumor microenvironment of the bone. Metastasis to the bone is a debilitating aspect of many cancers, including breast cancer, where it is a preferred site of metastasis that results in bone loss. Breast cancer cells release osteolytic factors that induce the breakdown of bone, which releases growth factors and calcium that create a vicious cycle of metastatic tumor growth. Using quantitative immunohistochemistry (AQUA) (n=134), we determined that high PRL-receptor expression in the primary tumor was associated with a shorter time to bone metastasis (PRLR AQUA Max Hazard ratio=1.04, 95% Hazard Ratio confidence limits 1.00-1.07, p=0.03/multivariable Cox proportional hazards model), indicating their treatment failure may be related to the PRL-receptor. We also identified the PRL-receptor on rare samples of matched primary and bone metastases. In an analysis of advanced breast cancer patients, we also detected the PRL-receptor in circulating tumor cells of the blood. PRL treatment of breast cancer cells induced osteoclast differentiation and bone lysis via presumed secreted factors, and interestingly these effects were abrogated by a PRL-receptor-antagonist (delta1-9-G129R-hPRL). We identified sonic hedgehog as part of the molecular mechanism by which PRL and the PRL-receptor induce breast cancer cells to directly promot...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Microenvironment and Immunotherapy: Poster Presentations - Proffered Abstracts Source Type: research