Tumour angiogenesis !
- Mechanism
A tumour cannot grow beyond a tiny size without its own blood vessels, so it learns to order new ones, mainly through VEGF.
Updated 2026-11-01
What it is
Oxygen and nutrients diffuse only a short distance, so a tumour larger than a few millimetres needs new vessels. The angiogenic switch occurs when pro-angiogenic signals (VEGF, FGF) outweigh inhibitors (thrombospondin-1, angiostatin), driven by hypoxia through HIF and by oncogenes. Tumour vessels are leaky, tortuous and disorganised, which helps metastasis and makes them a target for anti-VEGF therapy.
Structure
- Glioblastoma shows microvascular (glomeruloid) proliferation and necrosis with pseudopalisading tumour cells.
- Clear cell renal carcinoma has a delicate, rich network of thin vessels around nests of clear cells.
- Hepatocellular carcinoma has arterialised blood supply, which explains its imaging pattern.
Step by step
- As a tumour grows, cells far from vessels become hypoxic.
- Hypoxia stabilises HIF-1 alpha, which enters the nucleus.
- HIF induces VEGF and other angiogenic factors; oncogenes add more.
- VEGF binds receptors on nearby endothelium, which sprouts and proliferates.
- Proteases clear a path; new capillaries grow into the tumour.
- The tumour now grows beyond its diffusion limit and gains access to the circulation.
Clinical notes
- Highly vascular tumours (renal cell carcinoma, hepatocellular carcinoma) often enhance in the arterial phase of imaging.
- Anti-angiogenic therapies include antibodies against VEGF and small molecules against VEGF receptors.
- Kaposi sarcoma, a vascular tumour linked to HHV-8, is a reminder that some tumours are made of vessels themselves.
Test yourself
Think of the answer, then tap the question to see it.
Which transcription factor links hypoxia to VEGF?
HIF-1 alpha, which is stabilised in hypoxia and induces VEGF.
Why is clear cell renal cell carcinoma so vascular?
Loss of VHL prevents HIF degradation, so HIF continuously induces VEGF and other angiogenic genes.
How does p53 loss favour angiogenesis?
p53 normally induces anti-angiogenic factors such as thrombospondin-1; without p53 the balance tips toward angiogenesis.
What are two adverse effects of anti-VEGF therapy?
Hypertension and impaired wound healing (also bleeding, thrombosis and proteinuria).
Related
- The hallmarks of cancer
- Invasion and metastasis: the metastatic cascade, step by step
- Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis
- Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know
Related conditions
- Renal cell carcinoma
- Glioblastoma
- Hepatocellular carcinoma
- Colorectal cancer
- Kaposi sarcoma
- Lung cancer
- Phaeochromocytoma
- Hereditary paraganglioma and pheochromocytoma (SDH)
Elsewhere in DurgiPedia
- Blood vessels: artery, vein and capillary layers
- Receptor tyrosine kinases
- Warburg effect (aerobic glycolysis in cancer)
- Local and humoral control of blood flow
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Angiogenesis Inhibitors (National Cancer Institute (NCI), 2026); VHL gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Metastatic Cancer: When Cancer Spreads (National Cancer Institute (NCI), 2026).
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Representative model, for educational purposes only.