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Breast cancer goes to bone, lung, liver and brain; prostate cancer to bone; colon cancer to liver; uveal melanoma almost only to liver. Paget's 1889 idea still holds: where a cancer spreads depends on both the seed (the cell's programme) and the soil (the organ's welcome). Each soil has its own vicious cycle, and some are druggable.
Blood flow anatomy sets first-pass organs (portal vein → liver for gut cancers; lung for most), but survival there is selective. Bone: tumour PTHrP, IL-11 and IL-6 induce osteoblast RANKL, activating osteoclasts that release matrix-bound TGF-β and IGF-1, which feed the tumour (the vicious cycle broken by bisphosphonates and denosumab; radium-223 targets the bone-forming surface); CXCL12-CXCR4 and osteomimicry attract seeds. Lung: tenascin C, periostin and VCAM1 support stem-like cells; SPARC and ID1 programmes. Liver: Kupffer-cell and stellate-cell activation, CREB-driven metabolic adaptation, low immune surveillance; PDAC and uveal melanoma (BAP1 loss) show strong hepatic tropism. Brain: astrocyte-mediated support via gap junctions and plasmin inhibition (see blood-brain barrier). Peritoneum: ascites, omental fat, mesothelial attachment (ovarian, gastric, appendiceal). Seed programmes are partly encoded by subtype (basal breast → lung and brain; luminal → bone; HER2 → brain; SCLC → brain). Clinically, tropism informs surveillance (brain MRI in ALK/HER2 disease), bone-modifying agents, metastasis-directed SBRT, and regional therapies (HIPEC, liver-directed radioembolisation).
Dandelion seeds fall everywhere, but only take root where the soil suits them. Bone is a greenhouse for breast and prostate seeds because the seeds can trick the gardeners (osteoclasts) into digging up food for them.
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