Metastasis begins when tumors invade into surrounding tissues. In breast cancer, the study of cell interactions has provided fundamental insights into this complex process. Powerful intravital and 3D organoid culture systems have emerged that enable biologists to model the complexity of cell interactions during cancer invasion in real-time. Recent studies utilizing these techniques reveal distinct mechanisms through which multiple cancer cell and stromal cell subpopulations interact, including paracrine signaling, direct cell-cell adhesion, and remodeling of the extracellular matrix. Three cell interaction mechanisms have emerged to explain how breast tumors become invasive: epithelial-mesenchymal transition, collective invasion, and the macrophage-tumor cell feedback loop. Future work is needed to distinguish whether these mechanisms are mutually exclusive or whether they cooperate to drive metastasis.
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