Abstract 2528: PDLIM2 expression in triple negative breast cancer stromal macrophages

Abstract

Abstract PDLIM2 is a PDZ-LIM domain protein expressed in hematopoietic and epithelial cells that regulates the stability of transcription factors including NFΚB, STATs and beta catenin. PDLIM2 function is associated with tumour suppression and also with the acquisition of a metastatic or epithelial mesenchymal transition (EMT) phenotype. We recently showed that PDLIM2 is more highly expressed in Triple Negative Breast Cancer (TNBC) tumours than in other breast cancer types or normal breast tissue, and that this is associated with active beta catenin in TNBC (1). Interestingly, in PDLIM2-positive TNBC tumours, PDLIM2 was also present in the tumour-associated stroma. However, whether stromal PDLIM2 expression contributes to TNBC cancer progression is unknown. To investigate this further we assessed the phenotype of PDLIM2-expressing stromal cells and determined that they most strongly represented a M2-like macrophage population. We then investigated the requirement for PDLIM2 in polarization towards either the M1 and M2-like macrophage phenotype using cultured bone marrow-derived macrophages from PDLIM2 knockout mice compared with wild type. This demonstrated that PDLIM2 is required for full adoption of IL-4-induced M2 macrophage polarization and function, including cell adhesion and migration. M1 polarization was less dependent on PDLIM2, although potential for activation of STATs and NFKB was similar in both macrophage populations.We conclude that high expression of PDLIM2 in TNBC influences the tumour microenvironment through the presence of an M2 macrophage population. Reference: (1) Cox, O. T., Edmunds, S. J., Simon-Keller, K., Li, B., Moran, B., Buckley, N. E., Bustamante-Garrido, M., Healy, N., O'flanagan, C. H., Gallagher, W. M., Kennedy, R. D., Bernards, R., Caldas, C., Chin, S. F., Marx, A. & O'Connor, R. 2019. Pdlim2 Is A Marker Of Adhesion And Beta-Catenin Activity In Triple-Negative Breast Cancer. Cancer Res, 79, 2619-2633. Citation Format: Orla T. Cox, Stephanie Ward, Emilie Tresse, Rosemary O'Connor. PDLIM2 expression in triple negative breast cancer stromal macrophages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2528.