Table 1.
Milestones in high-resolution/throughput technologies in metastasis research.
Fig 1.
Single-cell insights into pre-metastatic niche formation, tumor dormancy, and reactivation dynamics.
Schematic representation illustrating critical events in metastatic niche formation and progression revealed by single-cell analyses. Primary tumors initiate the creation of pre-metastatic niches (PMNs) through the release of tumor-derived exosomes and factors, which recruit myeloid-derived cells and induce stromal remodeling in distant tissues, establishing an immunosuppressive and fibrotic microenvironment prior to tumor cell arrival. Upon arrival, disseminated tumor cells may enter dormancy, regulated by niche interactions involving immune and vascular cells. Dormant cells are maintained by interactions with stable vasculature, immune surveillance, and signaling pathways such as Jagged-1/Notch, but can reactivate when interacting with niche cells. ECM, extracellular matrix; MMP, matrix metalloproteinase; NET, neutrophil extracellular trap.
Fig 2.
Divergent and convergent mechanisms in metastatic colonization.
A. Tissue-specific mechanisms underlying metastatic colonization. Disseminated tumor cells (DTCs) engage in distinct interactions with organ-resident cells upon arrival at distant sites. Cancer cells adaptively reprogram the local environment to facilitate survival and expansion. For example, in bone, tumor-secreted cytokines disrupt osteoblast–osteoclast homeostasis, promoting a cycle of bone remodeling and tumor growth. Such adaptations depend on both tissue-specific features and intrinsic tumor properties. B. Shared mechanisms facilitating metastatic colonization. DTCs commonly employ strategies to evade immune detection, including recruitment of immunosuppressive cell populations, suppression of natural killer and T cell functions, and intrinsic metabolic reprogramming. These shared mechanisms are broadly conserved across diverse cancer types and metastatic sites. BBB, blood–brain barrier; CTL, cytotoxic T lymphocyte; ECM, extracellular matrix; MDSC, myeloid-derived suppressor cell; MMP, matrix metalloproteinase; NET, neutrophil extracellular trap; OXPHOS, oxidative phosphorylation; TH1, T helper 1 cell; TME, tumor microenvironment; Treg, regulatory T cell.