LRP-1 a key modulator of TBNC progression
Résumé
Triple-negative breast cancers (TNBC) are a very aggressive subtype of breast cancer with high metastatic potential; they do not respond to hormone therapy and few targeted therapies are available. During metastatic dissemination, tumor cells undergo a cascade of events including invasion of surrounding tissues, followed by blood vessels intravasation and extravasation mechanisms. We focused on molecular deciphering mediated by the LRP-1 receptor (Low Density lipoprotein Receptor-related Protein 1) in breast tumor progression using two cell lines of CSTN (HS578-T and 4T1). Performing 2D and 3D invasion tests demonstrates that LRP-1 KO TNBC cells are less invasive than control cells. Cell migration assays and atomic force microscopy (AFM) studies demonstrated that the loss of LRP-1 is accompanied by a decrease in the migratory capacities of cells as well as a decrease in their elasticity. HES staining of spheroid sections demonstrates that the loss of LRP-1 induces structural modifications of the spheroids as well as an increase in the necrotic area. In vivo, syngeneic grafts highlight the protumoral role of LRP-1, as well as its ability to regulate intratumoral lymphocyte infiltration. Taken together, these results highlight the pro-tumor role of LRP-1 in TNBC models via the regulation of the migratory and invasive capacities of tumor cells, and its ability to modulate immune cell populations within the tumor microenvironment.
| Origine | Fichiers produits par l'(les) auteur(s) |
|---|