Cancer-associated fibroblasts: Key criminals of tumor pre-metastatic niche

Cancer-associated fibroblasts (CAFs) are abundant and important components of the tumour mesenchyme, and have been extensively studied for their role in primary tumours. CAFs provide biomechanical support for tumour cells and play key roles in immunosuppression and tumour metastasis. CAFs can promote epithelial-mesenchymal transition (EMT) of the primary tumour by secreting extracellular vesicles (EVs), increasing adhesion to tumour cells, remodelling the extracellular matrix (ECM) of the primary tumour, and changing its mechanical stiffness, which provides a pathway for tumour metastasis. Moreover, CAFs can form cell clusters with circulating tumour cells (CTCs) to help them resist blood shear forces and achieve colonisation of distant host organs. Recent studies have revealed their roles in pre-metastatic niche (PMN) formation and prevention. In this review, we discuss the role of CAFs in PMN formation and therapeutic interventions targeting PMN and CAFs to prevent metastasis.