{"entity":{"id":"organ-tropism-seed-soil","kind":"pathway","name":"Organ tropism: seed and soil","aka":[],"tldr":"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.","summary":"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).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Seed_and_soil_hypothesis","links":[{"label":"Obenauf & Massagué, Surviving at a distance: organ-specific metastasis (Trends Cancer 2015)","url":"https://doi.org/10.1016/j.trecan.2015.07.009"}],"tags":["mechanism","mechanics-atlas"],"related":[],"cancers":["prostate","breast-hr-positive","colorectal","uveal-melanoma","ovarian"],"sections":[],"technologies":["bone-modifying-agents","sbrt","hipec","radioembolisation-tare","liver-transplant-oncology","whole-body-mri","psma-pet"],"targets":["cxcr4","psma","her2","alk"],"drugs":["radium-223","pluvicto","tucatinib","lorlatinib"],"companies":[],"institutions":[],"pathways":["metastatic-cascade","pre-metastatic-niche","blood-brain-barrier-metastasis","tgf-beta","tumor-dormancy"],"terms":["oligometastatic","peritoneal-metastasis","her2-brain-metastases","pam50","blood-brain-barrier"],"trials":[],"people":[],"bottlenecks":["b-metastasis-biology"],"keyPapers":["paper-obenauf-trends-cancer"],"journals":[],"dependsOn":[],"notes":[],"analogy":"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.","nodes":[{"id":"ctc","label":"CTC (seed programme)","x":12,"y":45},{"id":"flow","label":"Blood-flow anatomy","x":12,"y":12},{"id":"bone","label":"Bone: RANKL vicious cycle","x":45,"y":12},{"id":"lung","label":"Lung: tenascin C, periostin","x":45,"y":38},{"id":"liver","label":"Liver: Kupffer, stellate cells","x":45,"y":64},{"id":"brain","label":"Brain: astrocytes, BBB","x":45,"y":90},{"id":"tgf","label":"TGF-β, IGF-1 released","x":78,"y":12},{"id":"growth","label":"Organ-specific colonisation","x":88,"y":55},{"id":"bma","label":"Denosumab, radium-223","x":78,"y":32},{"id":"regional","label":"SBRT, HIPEC, TARE","x":88,"y":88}],"edges":[{"from":"flow","to":"ctc","type":"activates"},{"from":"ctc","to":"bone","type":"activates"},{"from":"ctc","to":"lung","type":"activates"},{"from":"ctc","to":"liver","type":"activates"},{"from":"ctc","to":"brain","type":"activates"},{"from":"bone","to":"tgf","type":"activates"},{"from":"tgf","to":"bone","type":"activates"},{"from":"tgf","to":"growth","type":"activates"},{"from":"lung","to":"growth","type":"activates"},{"from":"liver","to":"growth","type":"activates"},{"from":"brain","to":"growth","type":"activates"},{"from":"bma","to":"bone","type":"inhibits"},{"from":"regional","to":"growth","type":"inhibits"}],"interventions":["Bone: denosumab and zoledronic acid break the vicious cycle; radium-223 and 177Lu-PSMA in bone-predominant prostate cancer","Brain-penetrant TKIs and surveillance MRI in HER2+ breast, ALK+ lung and SCLC","Regional therapy for organ-confined spread: HIPEC (peritoneum), radioembolisation and liver transplant (liver), SBRT for oligometastases","Tropism-aware adjuvant trials and exosome profiling to predict relapse site"]},"route":"/pathways/organ-tropism-seed-soil/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"ovarian","kind":"cancer","name":"Ovarian cancer","route":"/cancers/ovarian/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"uveal-melanoma","kind":"cancer","name":"Uveal melanoma","route":"/cancers/uveal-melanoma/"}],"technology":[{"id":"bone-modifying-agents","kind":"technology","name":"Bone-modifying agents (bisphosphonates, denosumab)","route":"/technologies/bone-modifying-agents/"},{"id":"hipec","kind":"technology","name":"HIPEC / PIPAC (intraperitoneal chemotherapy)","route":"/technologies/hipec/"},{"id":"liver-transplant-oncology","kind":"technology","name":"Liver transplantation for cancer (Milan criteria and beyond)","route":"/technologies/liver-transplant-oncology/"},{"id":"psma-pet","kind":"technology","name":"PSMA PET","route":"/technologies/psma-pet/"},{"id":"radioembolisation-tare","kind":"technology","name":"Radioembolisation (TARE / SIRT, yttrium-90)","route":"/technologies/radioembolisation-tare/"},{"id":"sbrt","kind":"technology","name":"SBRT / SABR (stereotactic radiotherapy)","route":"/technologies/sbrt/"},{"id":"whole-body-mri","kind":"technology","name":"Whole-body MRI","route":"/technologies/whole-body-mri/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"},{"id":"cxcr4","kind":"target","name":"CXCR4","route":"/targets/cxcr4/"},{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"},{"id":"psma","kind":"target","name":"PSMA","route":"/targets/psma/"}],"drug":[{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"},{"id":"tucatinib","kind":"drug","name":"Tucatinib","route":"/drugs/tucatinib/"}],"pathway":[{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"blood-brain-barrier-metastasis","kind":"pathway","name":"The blood-brain barrier & brain metastasis","route":"/pathways/blood-brain-barrier-metastasis/"},{"id":"metastatic-cascade","kind":"pathway","name":"The metastatic cascade","route":"/pathways/metastatic-cascade/"},{"id":"pre-metastatic-niche","kind":"pathway","name":"The pre-metastatic niche","route":"/pathways/pre-metastatic-niche/"},{"id":"theories-of-cancer","kind":"pathway","name":"Theories of cancer: how the ideas connect","route":"/pathways/theories-of-cancer/"},{"id":"tumor-dormancy","kind":"pathway","name":"Tumour dormancy","route":"/pathways/tumor-dormancy/"}],"term":[{"id":"blood-brain-barrier","kind":"term","name":"Blood-brain barrier (BBB)","route":"/terms/blood-brain-barrier/"},{"id":"her2-brain-metastases","kind":"term","name":"HER2-positive brain metastases","route":"/terms/her2-brain-metastases/"},{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","route":"/terms/oligometastatic/"},{"id":"pam50","kind":"term","name":"PAM50 / intrinsic subtypes","route":"/terms/pam50/"},{"id":"peritoneal-metastasis","kind":"term","name":"Peritoneal metastasis","route":"/terms/peritoneal-metastasis/"},{"id":"seed-and-soil-hypothesis","kind":"term","name":"Seed and soil hypothesis of metastasis (Paget)","route":"/terms/seed-and-soil-hypothesis/"}],"bottleneck":[{"id":"b-metastasis-biology","kind":"bottleneck","name":"Metastasis is understood least and studied last","route":"/bottlenecks/b-metastasis-biology/"}],"paper":[{"id":"paper-obenauf-trends-cancer","kind":"paper","name":"Surviving at a Distance: Organ-Specific Metastasis","route":"/key-papers/paper-obenauf-trends-cancer/"}]}}