AMED3001 Cancer
Tumour Structure, the Microenvironment & Metastasis
Week 2 turns from the cancer cell to its ecosystem and its spread. It covers the tumour microenvironment (TME) — the cancer-associated fibroblasts, tumour-associated macrophages, immune cells, vasculature and extracellular matrix around the tumour — and then the ordered invasion-metastasis cascade that causes more than 90% of cancer deaths. Metastasis, EMT and the TME are high-value short-answer and diagram topics in the mid-semester quiz and the final (50%, confirm on Canvas).
What this chapter covers
- 01Tumour microenvironment (TME): cancer cells + non-cancer cells + extracellular matrix + signalling molecules
- 02Cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs: M1-like inflammatory vs M2-like tumour-supporting)
- 03Cancer stem cells: quiescent/slow-cycling, therapy-resistant, can rebuild a whole tumour
- 04Tumour angiogenesis and abnormal leaky vasculature → hypoxia, acidity, high interstitial fluid pressure
- 05Hot vs cold tumours: CD8+ T-cell infiltration and immune-checkpoint activation
- 06The invasion-metastasis cascade in order: local invasion → intravasation → survival in circulation → extravasation → colonisation
- 07EMT (epithelial-to-mesenchymal transition): loss of E-cadherin, driven by Snail, Slug, Twist, ZEB1
- 08Organ tropism: physical entrapment vs receptor-ligand homing (CXCR4/CXCL12); the seed-and-soil hypothesis
The invasion-metastasis cascade, step by step
- +1Local invasion — the cell breaches the basement membrane and moves into surrounding stroma; capability: EMT with loss of E-cadherin and MMP-mediated matrix degradation.
- +1Intravasation — entry into a blood or lymphatic vessel; capability: increased motility and neoangiogenesis providing leaky vessels to enter.
- +1Survival in the circulation — the circulating tumour cell must resist anoikis, shear stress and NK-cell killing (e.g. by forming platelet emboli).
- +1Arrest and extravasation — arrest at a distant capillary bed (physical entrapment or CXCR4–CXCL12 receptor-ligand homing) then exit the vessel; capability: vascular hyperpermeability factors (VEGF, MMPs).
- +1Colonisation — survive and proliferate in the foreign tissue to form a micrometastasis and then a clinically detectable macrometastasis; capability: a compatible ‘soil’ (seed-and-soil) and often MET, the reverse of EMT.
Key terms
- Tumour microenvironment (TME)
- The ecosystem around tumour cells — fibroblasts (esp. CAFs), immune cells, endothelial cells, pericytes and the extracellular matrix — that dynamically interacts with the tumour and shapes its growth and treatment response.
- Cancer-associated fibroblast (CAF)
- An activated fibroblast in the TME that remodels the matrix, secretes soluble factors (TGF-β, VEGF, IL-6, CXCL12) and can suppress T-cell function, supporting tumour growth.
- Tumour-associated macrophage (TAM)
- A macrophage in the TME that polarises between M1-like (inflammatory) and M2-like (tumour-supporting, immunosuppressive) states; M2-like TAMs promote angiogenesis by secreting VEGF-A.
- EMT
- Epithelial-to-mesenchymal transition: epithelial cells lose E-cadherin and gain a motile mesenchymal phenotype, driven by transcription factors Snail, Slug, Twist and ZEB1; MET is the reverse, used during colonisation.
- Invasion-metastasis cascade
- The ordered sequence of local invasion, intravasation, survival in the circulation, extravasation and colonisation by which a primary tumour seeds distant metastases.
- Seed and soil
- Stephen Paget's hypothesis that metastases form only where disseminated tumour cells (seeds) find a compatible microenvironment (soil), explaining organ-specific patterns of spread.
Tumour Structure, the Microenvironment & Metastasis FAQ
Why is metastasis, not the primary tumour, the main cause of cancer death?
More than 90% of cancer deaths are due to metastases rather than the primary tumour, because disseminated disease is systemic and hard to remove surgically. That is why the invasion-metastasis cascade and EMT are heavily examined.
Which cells in the TME promote angiogenesis?
Tumour-associated macrophages (M2-like) and CAFs secrete VEGF-A, driving the abnormal, leaky new vessels that supply the tumour — a favourite MCQ. Those disorganised vessels also cause hypoxia and high interstitial fluid pressure.
What is lost during EMT and why does it matter?
E-cadherin, the key epithelial adhesion molecule, is lost, letting cells detach and become motile; the switch is driven by Snail, Slug, Twist and ZEB1. Loss of E-cadherin is the single fact most likely to be asked about EMT.
Can AI help me memorise the invasion-metastasis cascade?
Yes — Sia can drill the cascade in order, pair each step with its molecular capability, and check your short-answer wording; it explains the method and checks your reasoning rather than doing the assessment for you.
Exam move
Learn the invasion-metastasis cascade as an ordered list and rehearse pairing each step with one capability — that structure is exactly how the short-answer marks are allocated. Keep the TME cell types straight (CAFs, M1 vs M2 TAMs, endothelial cells, ECM) and remember the two organ-tropism theories with the CXCR4/CXCL12 example. Because this material recurs in the mid-semester quiz and the final, practise a clean cascade diagram from memory. Ask Sia to test the order and the EMT transcription factors when they slip; confirm details on Canvas.
Working through Tumour Structure, the Microenvironment & Metastasis in AMED3001? Sia is AskSia’s AI Biology tutor — ask any AMED3001 Tumour Structure, the Microenvironment & Metastasis question and get a clear, step-by-step explanation grounded in how AMED3001 is taught and assessed. Read this chapter free, then take your hardest questions to Sia.
