Pathophys 4

Question 1

What is metastasis?

Answer 1

The process by which cancer spreads from the place at which it first arose as a primary tumour to distant locations in the body

Question 2

What are the factors that increase the likelihood of metastasis?

Answer 2

1-tumour size
2-Age of tumour
3-Differentiation status of the tumour
4-Certain cell types more likely to metastasise e.g saarcomas

Question 3

what are the two ways the cancer spreads?

Answer 3

1-lymphatics

2-Heamatogenous spread

Question 4

What occurs in the heamatogenous spread?

Answer 4

tumour cells infililtrate into blood vessels and spread thorugh the circulation, may form secondary deposits by passing through: the pulmonary veins, the portal veins, and the systemic veins

Question 5

What occurs in Lymphatics?

Answer 5

Neoplastic cells infiltrate into lymphatic ducts which then are carried to draining lymph nodes (forming a tumour deposit) then spread further into the lymphatics

Question 6

What are the 10 steps of Metastasis?

Answer 6

1. Transformation
2. Angiogenisis
3. Motility
4. Embolism
5. Arrest in capillery beds
6. Adherence
7. Extravasation into organ parenchyma
8. Response to micro enviroment
9. Tumour cell proliferation
10. Metastasis

Question 7

What does angiogenisis require?

Answer 7

endothelial cell proliferation
Changes in adhesion
Cell migration
Detachment of pericytes from blood vessel wall
Degradation of the vascular basement membrane
Alterations of cell to cell and cell to matrix adhesions
Migration of endothelial cells

Question 8

If angiogenisis did not exist what would happen?

Answer 8

tumour size would be limited

Question 9

What are examples of stimulators of angiogenisis?

Answer 9

Growth factors:VEGF=Vascular Endothelial Growth Factor, FGF,EGF,PGF
Cytokines:IL8, TNFa, TGF
Small molecules:adenosine, nicotinamide

Question 10

VEGF function?

Answer 10

Induces proliferation of vascular epithelial cells
Stimulates endothelial cells to release MMPs
Increase blood vessel permeability (aiding the degradation of the basal membrane)

Question 11

3 examples of angiogenisis?

Answer 11

Thrombospondin-1
Angiostatin
Endostatin
A tumour cell can cause a shift in the balance towards pro-angiogenisis

Question 12

Cancer cell motility has significant roles in metastasis, why?

Answer 12

Changes in intergrin receptor subtypes are associated with cancer progression
Expression of proteases that degrade the protein components of the basal laminae and the ECM (MMPs) are required for cell migration