01Step by step
Metastasis is a gauntlet: local invasion → intravasation (entering blood or lymph) → survival in circulation → arrest and extravasation → micrometastasis → colonization. It's wildly inefficient — millions of cells shed daily, but very few form tumors.
In the bloodstream, cells face shear forces and immune attack; many coat themselves with platelets for protection.
02Seed and soil
In 1889 Stephen Paget proposed the seed and soil hypothesis: metastases form where the 'soil' suits the 'seed'. Breast cancer favors bone, liver, lung and brain; prostate cancer favors bone; colon cancer spreads first to the liver via the portal vein.
Primary tumors can prepare a pre-metastatic niche by releasing exosomes and factors that remodel distant tissue before cells arrive. Some disseminated cells sit dormant for years before waking — why breast cancer can recur a decade later.