Crosstalk between stromal and breast tumour cells in the context of tamoxifen resistance

Abstract

Breast cancer, being the most common malignancy and a leading cause of cancer-related death in women worldwide, presents a significant challenge in treatment, especially in cases of tamoxifen resistance. This research focuses on the interaction between control MCF7 cells (MCF7c) and tamoxifen-resistant MCF7 (TamR) cells with key cellular components in the tumour microenvironment (TME), such as mesenchymal stem cells (MSCs), normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs). Bidirectional communication and reciprocal modulation were observed among these cell types, with stromal cells promoting tumour progression and therapy resistance. Lipocalin-2 (Lcn2) was identified as a key mediator in tamoxifen resistance, with its inhibition showing promising effects in restoring treatment sensitivity. Additionally, the biomechanical properties of cell co-cultures were explored using atomic force microscopy (AFM) during international collaboration. These findings underscore the importance of understanding cellular communication and the microarchitecture of the tumour microenvironment in breast cancer and treatment resistance, opening new perspectives for more effective therapies.