Pleiotrophin drives a pro-metastatic immune niche within the breast tumor microenvironment

Here, we evaluated the effect of Pleiotrophin (PTN) depletion on tumor microenvironment. For this, we utilized a mouse monoclonal antibody against PTN, 3B10. We tested its therapeutic efficacy in 2 mouse breast cancer models, 4T1 (orthotopic, 4th mammary fat pad) and MMTV-PyMT (genetic model). Tumors from control IgG(C44) treated and 3B10 treated mice were sent for RNA sequencing to evaluate transcriptional changes. Additionally, PTN was knocked down in E0771 and E0771-LG syngeneic breast cancer lines. To evaluate transcriptional changes due to PTN depletion, shCtrl and PTN KD cells from E0771 and E0771-LG were evaluated by RNA sequencing. Overall, our results from these 4 sets of experiments show that depletion or blocking PTN results in inflammation related transcript changes suggesting function of PTN in immune regulation. Breast cancer tumors (4T1 & MMTV-PyMT) or cells (E0771 or E0771-LG) were treated with 3B10 or depleted of PTN.