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; T H 1, T helper 1 cell; TME, tumor microenvironment; Treg, regulatory T cell.