Surviving at a Distance: Organ-Specific Metastasis

The pattern of affected organs in metastasis is variable depending on the tumor of origin, indicating that intrinsic cancer cell traits, the physical accessibility of target organs, and the composition of host-organ microenvironments are important determinants of distant metastasis. Metastasis is an inefficient process in which few cells succeed at reestablishing a tumor at a distant organ. Organ-specific metastasis involves cancer cell interactions with the host microenvironment, including activation of paracrine cytokine loops, modification of the host cellular composition, and alteration of extracellular matrix structures. Immune cell evasion, association with a supportive niche, and the ability to amplify survival pathways, often achieved through interaction with the stroma, are essential for successful metastatic colonization. The clinical manifestation of metastasis in a vital organ is the final stage of cancer progression and the main culprit of cancer-related mortality. Once established, metastasis is devastating, but only a small proportion of the cancer cells that leave a tumor succeed at infiltrating, surviving, and ultimately overtaking a distant organ. The bottlenecks that challenge cancer cells in newly invaded microenvironments are organ-specific and consequently demand distinct mechanisms for metastatic colonization. We review the metastatic traits that allow cancer cells to colonize distinct organ sites. The clinical manifestation of metastasis in a vital organ is the final stage of cancer progression and the main culprit of cancer-related mortality. Once established, metastasis is devastating, but only a small proportion of the cancer cells that leave a tumor succeed at infiltrating, surviving, and ultimately overtaking a distant organ. The bottlenecks that challenge cancer cells in newly invaded microenvironments are organ-specific and consequently demand distinct mechanisms for metastatic colonization. We review the metastatic traits that allow cancer cells to colonize distinct organ sites.