9 metastasis Flashcards
What is metastasis?
the spread of a tumour from the primary organ to distant sites in the body, making cancer more difficult to treat and responsible for most cancer-related deaths.
Why is metastatic disease difficult to treat?
It involves multiple steps, heterogeneity among tumour cells, and resistance to therapy, requiring more targeted treatments.
What are the primary routes of metastatic spread?
Blood vessels (haematogenous), lymphatic system, and body cavity movement (peritoneal or pleural spread).
How does lung metastasis cause mortality?
It impairs respiratory function, leading to breathing difficulties and organ failure.
What are the effects of liver metastases?
Liver metastases can cause bile duct obstruction, liver failure, and altered metabolism.
Why is pancreatic metastasis dangerous?
It disrupts insulin production, leading to diabetes-like symptoms, and affects digestive enzyme secretion.
How does bone and bone marrow metastasis lead to complications?
It disrupts haematopoiesis, leading to anaemia, infections, and bone marrow failure.
What are the consequences of brain metastases?
They can cause loss of neurological function, seizures, and brain herniation.
How does heart metastasis impact the body?
It can cause cardiac failure, arrhythmias, and vasospasm, potentially leading to sudden death.
What is the effect of metastases in the kidneys?
They cause kidney dysfunction, failure, and an increased risk of sepsis due to ureteric obstruction.
How do digestive tract metastases contribute to mortality?
They impair digestion, nutrient absorption, and can cause perforation, leading to severe infections.
What are the main steps of metastasis?
Transformation
→ Angiogenesis
→ Mobility & Invasion
→ Embolism & Circulation
→ Arrest in Capillary Beds
→ Adherence
→ Extravasation
→ Response to Microenvironment
→ Tumour Cell Proliferation
→ Metastases Formation
→ Secondary Metastases.
What happens during the transformation step?
Normal cells acquire mutations that enable uncontrolled growth and invasion of surrounding tissues.
Why is angiogenesis important in metastasis?
Tumours need blood vessels to supply oxygen and nutrients for growth and allow entry into circulation.
What enables cancer cells to become mobile and invade tissues?
Changes in adhesion molecules, cytoskeletal reorganisation, and increased protease activity help tumour cells move and invade.
What occurs during embolism and circulation?
Cancer cells enter the bloodstream or lymphatic system, often protected by platelets, to avoid immune destruction.
How do tumour cells arrest in capillary beds?
They adhere to endothelial cells using adhesion molecules and become trapped in narrow capillaries.
What is extravasation in metastasis?
The process where cancer cells exit the bloodstream and invade organ parenchyma to establish a secondary tumour.
Why is the tumour microenvironment important for metastasis?
It provides essential signals, nutrients, and growth factors that allow metastatic cells to survive and proliferate.
What is metastasis of metastases?
Secondary tumours can also spread to new sites, forming additional metastatic tumours.
How does colorectal cancer metastasise?
It spreads through lymphatic (to lymph nodes), transcoelomic (to peritoneum), and haematogenous (to liver) routes.
Why is the liver a common site for blood-borne metastases?
It acts as a first-pass organ for venous blood, filtering tumour cells from circulation.
What are common secondary sites for breast cancer metastases?
Bone, liver, lungs, and lymph nodes (especially in the armpit).
What is the “Seed and Soil” hypothesis?
It suggests tumour cells (seeds) prefer specific environments (soil) that provide favourable conditions for growth.
What is the mechanical theory of metastasis?
It proposes that the pattern of blood flow determines where tumour cells arrest and grow.
Why is metastasis inefficient?
Most metastatic cells die in transit, and only a small fraction successfully colonise distant organs.
Why is metastasis poorly understood at the molecular level?
It involves multiple genetic alterations, heterogeneity, and complex interactions with the tumour microenvironment.
What are key factors affecting tumour heterogeneity?
Clonal diversity, microenvironment interactions, spatial organisation, differentiation, metastasis, and resistance mechanisms.
Why are adhesion molecules crucial in metastasis?
They regulate cancer cell migration, invasion, and extravasation.
What are the four main classes of cell adhesion molecules (CAMs)?
Integrins, Cadherins, Selectins, and Immunoglobulin family proteins.
How does integrin expression change in metastasis?
Some integrins are lost (e.g., α2β1 in breast cancer), while others increase (e.g., αvβ3 in melanoma).
What is the role of proteases in metastasis?
They degrade extracellular matrix (ECM) components, aiding tumour invasion and migration.
How do tumour cells evade immune detection?
By downregulating MHC class I, inducing immune cell apoptosis, and releasing immunosuppressive cytokines.
What is the role of immune checkpoint ligands in cancer immune evasion?
They prevent T cells from mounting an effective immune response against the tumour.
What are the three major classes of proteases involved in metastasis?
Metalloproteinases (MMPs), Serine proteases, and Cysteine proteases.
What is the role of matrix metalloproteinases (MMPs) in metastasis?
They degrade ECM, promote angiogenesis, and facilitate tumour invasion.
How do proteases remodel the tumour microenvironment?
By degrading ECM proteins, releasing growth factors, and activating other proteases.
What molecules regulate cancer cell migration?
Integrins, Rho and Rac GTPases, cytoskeletal proteins, and ECM components.
How do chemokines contribute to metastasis?
They create paracrine signalling loops that guide tumour cell migration (e.g., CXCL12-CXCR4).
What in vitro models are used to study metastasis?
Tumour-derived cell lines and functional assays for proliferation, adhesion, and migration.
What in vivo models help study metastasis?
Animal models and imaging techniques to track tumour spread.
What is the first step in metastasis?
Transformation, where normal cells acquire genetic mutations that lead to uncontrolled proliferation and tumour formation.
What types of mutations contribute to tumour transformation?
Mutations in oncogenes (e.g., RAS, MYC), tumour suppressor genes (e.g., TP53, RB1), and DNA repair genes.
How does genomic instability affect metastasis?
It increases mutation rates, leading to tumour heterogeneity and adaptation to different environments.
Why is angiogenesis essential for metastasis?
It supplies oxygen and nutrients to the growing tumour and provides a route for cancer cells to enter circulation.
What key factors regulate tumour angiogenesis?
VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), and HIF-1α (hypoxia-inducible factor).
How do tumours promote blood vessel growth?
By releasing pro-angiogenic factors and suppressing anti-angiogenic signals.
What is local invasion in metastasis?
The ability of cancer cells to break through the basement membrane and invade surrounding tissues.
What molecules enable cancer cell motility?
Integrins, cadherins, actin cytoskeleton regulators, and ECM-degrading enzymes (MMPs).
How do cancer cells degrade the extracellular matrix (ECM)?
By secreting matrix metalloproteinases (MMPs) and other proteases that break down ECM components.
What role does epithelial-mesenchymal transition (EMT) play in invasion?
EMT allows epithelial tumour cells to gain mesenchymal properties, increasing motility and invasion capacity.
What is intravasation?
The process where tumour cells enter blood or lymphatic vessels.
How do tumour cells penetrate blood vessels?
They degrade the endothelial basement membrane and interact with endothelial cells to facilitate entry.
What role do tumour-associated macrophages (TAMs) play in intravasation?
TAMs produce cytokines and proteases that help tumour cells breach the vessel wall.
What challenges do circulating tumour cells (CTCs) face?
Immune attacks, shear stress from blood flow, and lack of attachment to the ECM.
How do tumour cells survive in circulation?
By forming emboli (clusters with platelets), expressing immune checkpoint ligands, and activating stress response pathways.
Why do some cancer cells prefer the lymphatic system over the bloodstream?
The lymphatic system has lower shear stress and a weaker immune response than the bloodstream.
What is extravasation in metastasis?
The process where circulating tumour cells exit the bloodstream and invade a distant organ.
How do tumour cells adhere to blood vessel walls at distant sites?
By using adhesion molecules like integrins and selectins.
What happens after tumour cells adhere to the endothelium?
They weaken endothelial junctions, migrate through the vessel wall, and invade surrounding tissue.
Why is colonisation the most inefficient step of metastasis?
Most tumour cells die due to lack of proper signals, immune attack, and inability to adapt to the new microenvironment.
What is required for successful colonisation?
The tumour cells must evade immune defences, modify the microenvironment, and acquire nutrients.
How do metastatic cells modify the new organ environment?
By recruiting stromal cells, inducing angiogenesis, and altering immune responses.
What defines a successful metastatic lesion?
It can proliferate, evade immune surveillance, and establish a supportive microenvironment.
What factors influence organ-specific metastasis?
Blood flow patterns, tumour cell receptor-ligand interactions, and local tissue conditions.
How do secondary metastases form?
Some metastatic cells spread again from the secondary site to new organs, continuing the cycle.
