LRP-1 (low-density lipoprotein receptor-related protein-1) receptor is a multifunctional endocytosis receptor that is part of the LDL receptor family. Due to its capacity to control the pericellular level of various growth factors and proteases, LRP-1 plays a crucial role in controlling the dynamics of the membrane proteome. LRP-1 overexpression in breast cancer, prompted us to take an interest in its involvement in tumor progression. An RNA interference strategy in MDA-MB-231 line was used, based on shRNA stable expression. In addition to integrated experimental strategies (in vitro and in vivo) through combined approaches of biochemistry, molecular biology, cell biology, multimodal preclinical imaging, proteomics allowed us to compare shLRP-1 MDA-MB-231 tumor conditioned media to shCtrl MDA-MB-231 tumor conditioned media in order to identify secreted molecular targets modulate by LRP-1 repression and thus provide a better understanding of its regulatory action within the TNBC microenvironment.