# Organ tropism: seed and soil

Source: https://onco.cc/pathways/organ-tropism-seed-soil/  
OnCo record `organ-tropism-seed-soil` (Pathway). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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).

## Fields

- Kind: Pathway
- Last checked: 2026-09-09
- Tags: mechanism; mechanics-atlas
- 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.
- 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Seed_and_soil_hypothesis
- Obenauf & Massagué, Surviving at a distance: organ-specific metastasis (Trends Cancer 2015): https://doi.org/10.1016/j.trecan.2015.07.009

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Uveal melanoma](https://onco.cc/cancers/uveal-melanoma/)
- technologies: [Bone-modifying agents (bisphosphonates, denosumab)](https://onco.cc/technologies/bone-modifying-agents/), [HIPEC / PIPAC (intraperitoneal chemotherapy)](https://onco.cc/technologies/hipec/), [Liver transplantation for cancer (Milan criteria and beyond)](https://onco.cc/technologies/liver-transplant-oncology/), [PSMA PET](https://onco.cc/technologies/psma-pet/), [Radioembolisation (TARE / SIRT, yttrium-90)](https://onco.cc/technologies/radioembolisation-tare/), [SBRT / SABR (stereotactic radiotherapy)](https://onco.cc/technologies/sbrt/), [Whole-body MRI](https://onco.cc/technologies/whole-body-mri/)
- targets: [ALK](https://onco.cc/targets/alk/), [CXCR4](https://onco.cc/targets/cxcr4/), [HER2](https://onco.cc/targets/her2/), [PSMA](https://onco.cc/targets/psma/)
- drugs: [Lorlatinib](https://onco.cc/drugs/lorlatinib/), [Lutetium-177 vipivotide tetraxetan](https://onco.cc/drugs/pluvicto/), [Radium-223 dichloride](https://onco.cc/drugs/radium-223/), [Tucatinib](https://onco.cc/drugs/tucatinib/)
- pathways: [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [The blood-brain barrier & brain metastasis](https://onco.cc/pathways/blood-brain-barrier-metastasis/), [The metastatic cascade](https://onco.cc/pathways/metastatic-cascade/), [The pre-metastatic niche](https://onco.cc/pathways/pre-metastatic-niche/), [Theories of cancer: how the ideas connect](https://onco.cc/pathways/theories-of-cancer/), [Tumour dormancy](https://onco.cc/pathways/tumor-dormancy/)
- terms: [Blood-brain barrier (BBB)](https://onco.cc/terms/blood-brain-barrier/), [HER2-positive brain metastases](https://onco.cc/terms/her2-brain-metastases/), [Oligometastatic disease](https://onco.cc/terms/oligometastatic/), [PAM50 / intrinsic subtypes](https://onco.cc/terms/pam50/), [Peritoneal metastasis](https://onco.cc/terms/peritoneal-metastasis/), [Seed and soil hypothesis of metastasis (Paget)](https://onco.cc/terms/seed-and-soil-hypothesis/)
- bottlenecks: [Metastasis is understood least and studied last](https://onco.cc/bottlenecks/b-metastasis-biology/)
- key papers: [Surviving at a Distance: Organ-Specific Metastasis](https://onco.cc/key-papers/paper-obenauf-trends-cancer/)

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