invasion and metastasis

Question 1

define cancer

Answer 1

• abnormal cells that divide uncontrollably
• in the absence of normal growth signals
• have the capacity to invade nearby tissues and spread elsewhere in the body

Question 2

define invasion

Answer 2

the ability of cancer cells to break through their original tissue boundaries and infiltrate nearby tissues.

Question 3

define metastasis

Answer 3

the process by which cancer cells spread from the original (primary) tumor site to distant parts of the body, forming new (secondary) tumors.

Question 4

outline the differences between invasion and metastasis

Answer 4

• invasion is the local spread of cancer into surrounding tissues, while metastasis is the spread to distant parts of the body through blood or lymphatic systems.
• invasion is the first step in the process of metastasis and is much less clinically significant whereas metastasis is the hallmark of advanced cancer

Question 5

what does the term carcinoma describe?

Answer 5

epithelial cancer

Question 6

Q: What are the benefits and drawbacks of passive and active immunization?

Answer 6

Passive Immunization

Benefits:
Immediate protection.
Useful for immunocompromised individuals.
No need for prior immune activation.
Drawbacks:
Short-lived (weeks to months).
No immune memory.
Risk of allergic reactions (e.g., serum sickness).
Expensive.

active immunisation:
benefits:
long-lasting immunity
development of immunilogical memory
herd immunity
cost-effective in the long run

drawbacks:
- delayed onset of protection
- adverse reactions
- booster requiremnts
- not always effective in immunocomprimised
- costly to develop

Question 7

Q: What is the difference between carcinoma in situ, invasive carcinoma, and metastatic carcinoma?

Answer 7

1. Carcinoma In Situ (CIS)

Definition: A pre-cancerous stage where abnormal cells are confined to the layer of tissue where they originated (epithelial tissue).
Characteristics:
Cells are abnormal but have not spread beyond the tissue of origin.
Considered to be localized and non-invasive.
Can often be treated successfully with surgery or other localized therapies.
Example: Ductal carcinoma in situ (DCIS) in the breast.
2. Invasive Carcinoma

Definition: Cancer that has spread beyond its original tissue (epithelium) into surrounding tissues.
Characteristics:
Tumor cells invade surrounding structures and may enter blood or lymphatic vessels.
More likely to grow, spread to nearby tissues, and require aggressive treatments like surgery, chemotherapy, or radiation.
Often classified by the extent of spread within local tissues.
Example: Invasive ductal carcinoma of the breast.
3. Metastatic Carcinoma

Definition: Cancer that has spread from the primary site to distant organs or tissues through the bloodstream or lymphatic system.
Characteristics:
Tumor cells establish secondary growths in organs away from the original site.
Often results in a more difficult-to-treat, advanced stage of cancer.
Indicates that the cancer has progressed beyond local and regional spread.
Example: Metastatic lung cancer spreading to the liver.
Key Differences:

CIS: Localized, non-invasive, pre-cancerous cells.
Invasive: Cancer cells have spread into surrounding tissues, but not yet to distant parts of the body.
Metastatic: Cancer has spread to distant organs, making it more challenging to treat.

Question 8

Q: Why is cancer invasion and metastasis clinically important?

Answer 8

• implications on grognostics - agressive vs advanced stage
• treatment options
• treatment monitoring
• impact and quality of life - social support

Question 9

outline the steps of the metastatic cascade

Answer 9

• invasion and migration
• angiogenesis and instravasation (survive in blood vessels)
• survival in the circulation and attachment to the endothelium
• extrasasation and colonosation

Question 10

explain the process of invasion and migration of the metastatic cascade.

Answer 10

• the epithelial cells undergo changes, making them act more like mesenchymal cells

ways this happens:
- lose awareness that theyre meant to attach to other cells and the basement membrane
- cytoskeleton gets rearranged
- secrete matrix metalloprotease to break down collagen to move easier through it and to provide an amino acid resourse

Question 11

outline the changes that occur to the epithelial cells during invasion and migration.

Answer 11

• polygonal to spindle like
• stable to loss of cell junctions
• rearrangement of actin cytoskeleton

Question 12

outline the step angiogenesis
and intravasation in the metaststic cascade

Answer 12

angiogenesis
- as tumour grows theres an increased oxygen requirement so the tumour releases VEGF signalling when it becomes hypoxic
- this stimulates new vessels to grow
- these are rapidly made, disorganised and fradgile meaning they often bleed

intravasation = the tumour moving from the tissue across epithelium into the blood
ways they do this:
- intrinsic properties - genes, metabolism ect
- mechanical cues such as the fluid pressure
- cellular microenvironement - immune cells respond and may chaperone them into circulation

Question 13

outline the step of survival in the bloodstream in the metastatic pathway.

Answer 13

• when tumour cells, the microenvironment, immune cells and collagen travel together, they have the best chances of survival
• however its very slim that the tumour cells are actually in this cluster with other cells - only 2-5% are in this composition
• this results in a lot of tumour cell death

Question 14

outline the extravasation and colonisation step of the metastatic cascade.

Answer 14

extravasation
- getting out of the blood supply
- then go form meesenchymal back to endothelial cells

collinisation
cancer cells will then either do 1 of 2 things:
1. immediately start dividing and create a metastatic deposit
2. enter dormant state / late metastatis and start dividing to forma metastasis maybe years later. melanoma, renal cell carcinoma and breast cancers all regularly do this and can sometimes sit undividing for years and only become problematic years later

Question 15

why is it useful to use blood tests to detect cancer?

Answer 15

10-30% of patients with early-stage cancer will have tumour cells detectable in their bloodstream

Question 16

name common sites for metastatis.

Answer 16

• lymph
• lung
• bone
• liver
• brain
• transcoelomic - cavity lined by mesothelioma eg abdomen

Question 17

when testicular cancer metastases via lymph, where does it go and why is this unusual.

Answer 17

• usually tumours when metastasing through the lymphatics go somewhere local except testicular cancer which will go either side of the aorta because this is where embryonically the testis developed from.

Question 18

name the routes of cancer spread.

Answer 18

Lymphatics
Blood vessels
Nerves
Transcoelomic through coelic epithelium
Iatrogenic - unintentionally by medical tratments or procedures

Question 19

in lymphatic travel during metastasis, why is the sentinel node an important concept.

Answer 19

• it is thought that if tumours are metastasing and travelling via lymph, the first place they will travel to is the sentinel lymph node so if cancer is suspected, this node is removed first

Question 20

Q: What is the process of local and distant spread of cancers?

Answer 20

1. Local Spread

Definition: Cancer’s direct invasion into surrounding tissues near the primary tumor.
Process:
Tumor Proliferation: Cancer cells multiply uncontrollably.
Breakdown of Barriers: Tumor cells secrete enzymes (e.g., matrix metalloproteinases) that degrade the extracellular matrix and basement membrane.
Migration: Cancer cells invade neighboring tissues via amoeboid or mesenchymal movement.
Characteristics:
Results in the gradual expansion of the tumor.
Can compress, damage, or invade nearby structures (e.g., blood vessels, nerves).
2. Distant Spread (Metastasis)

Definition: Cancer cells travel to and establish growth in distant organs or tissues.
Process:
Intravasation: Cancer cells enter the bloodstream or lymphatic system.
Survival in Circulation: Tumor cells evade immune detection and resist shear stress in the blood.
Extravasation: Cells exit vessels and invade distant tissues.
Colonization: Cancer cells adapt to the new microenvironment and form secondary tumors.
Preferred Sites:
Metastases often occur in organs with high blood flow or favorable environments, e.g., liver, lungs, brain, and bones.

Question 21

Q: What factors promote cancer invasion and metastasis?

Answer 21

1. Cellular Factors

• Genetic Mutations in oncogenes and tumor suppressor genes - enhance tumor cell aggressiveness.
• Epithelial cells lose adhesion properties and gain migratory abilities.
• Cytoskeletal Remodeling enables cancer cells to move and invade.

2. Biochemical Factors
   - Proteolytic Enzymes - Matrix metalloproteinases
   Growth Factors and Cytokines - like VEGF and TGF-β stimulate angiogenesis, migration, and immune evasion.
3. Microenvironmental Factors
   - Tumor Microenvironment:
   Hypoxia triggers secretion of angiogenic factors like HIF-1α.
   Tumor-associated macrophages (TAMs) secrete proteases and growth factors
   Tumor cells evade detection by downregulating MHC molecules or secreting immunosuppressive factors (e.g., PD-L1).
4. Physical Factors
   - Increased Interstitial Pressure - Promotes cell migration
   - Vascularization near tumors provides routes for metastasis.

Question 22

Q: What factors inhibit cancer invasion and metastasis?

Answer 22

• Tumor Suppressor Genes
• Cell Adhesion Molecules
• Intrinsic apoptosis mediated by BAX and BAK.
• Protease Inhibitors block matrix metalloproteinases
• Cytotoxic T cells, natural killer (NK) cells, and macrophages destroy metastatic cells.
• Anti-Angiogenic Factors
• Intact ECM provides a physical barrier against invasion.
• IFN-γ activate immune cells to suppress tumor growth.
• microRNAs suppress metastasis-related genes.
• Methylation or acetylation of genes prevents activation of metastatic pathways.