Tumours are surrounded by the stroma, which includes extracellular matrix (ECM) components and non-cancer cells. Stromal cancer-associated fibroblasts (CAFs) are fibroblasts that have been ‘re-programmed’ by tumour-derived signals, often to enable growth and invasion of cancer cells away from the primary tumour. However, more information is needed on how crosstalk between CAFs and cancer cells facilitates these behaviours, particularly in aggressive forms of breast cancer exhibiting independent 3D migration and ECM degradation. In this study (Goliwas et al., 2023), Cynthia Reinhart-King and colleagues report that CAFs can transfer mitochondria to neighbouring breast cancer cells to enhance the oxidative phosphorylation of cancer cells. Using a co-culture system, they observe tagged mitochondria originating from CAFs travelling into unlabelled cancer cells via tunnelling nanotube membrane contacts. Cancer cells co-cultured with CAFs show increased migration and invasion into the ECM compared to monocultures. Strikingly, cancer cells containing CAF-derived mitochondria exhibit increased invasion and retain higher rates of mitochondrial respiration even after CAFs have been removed, suggesting that the reverse Warburg effect and other traditional cancer cell-CAF interactions cannot fully explain the pro-invasion effects of CAFs. Further exploration of the mechanisms of mitochondrial transfer might help identify new therapeutic approaches to disrupt tumour-stroma communication that fuels aggressive breast cancers.
