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The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited

Abstract

Researchers have been studying metastasis for more than 100 years, and only recently have we gained insight into the mechanisms by which metastatic cells arise from primary tumours and the reasons that certain tumour types tend to metastasize to specific organs. Stephen Paget's 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the 'seeds') and specific organ microenvironments (the 'soil') still holds forth today. It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis. How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?

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Figure 1
Figure 2: The main steps in the formation of a metastasis.
Figure 3: Sequential steps in the pathogenesis of cancer metastasis.
Figure 4: Metastatic heterogeneity.

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DATABASES

cancer.gov

breast cancer

colon cancer

melanoma

ovarian cancer

renal-cell carcinoma

FURTHER INFORMATION

National Cancer Institute's questions and answers about metastatic cancer

Glossary

ASCITES

The intraperitoneal accumulation of transudate (watery fluid).

CINEPHOTOMICROGRAPHY

The process of recording (making movies of) the movements of objects that are viewed through a microsope.

CROTON OIL

Oil that is produced from the seed of the tree Croton tiglium. It is an irritant that is used as a tumour promoter.

PERITONEOVENOUS SHUNTS

Drainage of ascitic fluids into the jugular vein through a tube.

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Fidler, I. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer 3, 453–458 (2003). https://doi.org/10.1038/nrc1098

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