1. Cancer metastasis Clara Farque (c.e.Farque@warwick.ac.uk)
Alex Hammant

2. What is invasion?
The ability of cells to break through normal barriers (e.g. basement membrane), and then spread.
Into surrounding tissue
In lymphatic/vascular channels
Malignant cell = ability to invade basement membrane and metastasise

3. What are cadherins and integrins?
Cadherins : glycoproteins between cells : maintain position and polarity
Integrins : glycoproteins between cells and stroma : anchoring
Malignant cells: reduced expression of integrins and cadherins : cells detach from each other and move

4. 1) What is a matrix metalloproteinase. 2)Name three families of MMPs
1) What is a matrix metalloproteinase? 2)Name three families of MMPs. 3) What counteract MMPs?
1) Enzymes which degrade extracellular matrix 2)
Collagenases : degrade Collagen I-III
Gelatinases : Collagen IV and gelatin
Stromelysins : Collagen IV and proteoglycans
3) Tissue Inhibitors of Metalloproteinases (TIMPS)

5. What is metastasis? What are the four routes of metastasis?
Ability of malignant cells to invade into lymphatics, blood vessels and cavities, and spread to distant (non contiguous sites)
Transcoelomic
Lymphatic
Blood stream
Surgical (post-transplant)

6. What are the common sites of metastatic spread (lymphatic, vascular, transcoelomic)
Lymphatic : local and distal lymph nodes
Vascular spread : lung, liver, bone and brain
Transcoelomic spread : Ovary, stomach, breast, lung

7. What are the steps of metastasis?
Black
Exclaimed
I’m
Inside
Potter
After
Escaping
Azkaban
Invade BM
Passage through ECM
Intravasation
Immune interaction
Platelet adhesion
Adhesion to endothelium
Extravasation
Angiogenesis

8. Name as many hallmarks as you can?
What happens first:
Genome Instability
Deregulating cellular energetics
How does it survive (and become ‘immortal’):
Self sustaining growth signals
Evade growth suppression
Limitless/endless replication
Avoid immune destruction
Resist cell death
Tumour promoting inflammation
How does it thrive:
Invasion and metastasis
Angiogenesis

9. What is the difference between primary and secondary metastasis?
Primary – site where the malignant neoplasm arises
Secondary – metastasis e.g. carcinoma that has spread to another organ

10. Which are the 3 cancers with the highest mortality rates in women?
Lung
Breasts
Bowel

11. Which are the 3 cancers with the highest mortality rates in men?
Lung
Prostate
Bowel

12. What is the tumour staging system in breast cancer?
TMN staging system.
T = the size of the Tumour
N = the Node involvement
M = Metastases
T1 = <2cm size
T2 = cm
T3 = skin and/ or chest wall involved
N0 = no axilliary nodes involved
N1 = mobile nodes involved
M0 = no metastases
M1 = demonstrable metastases

13. What is tumour grading?
The grading is the degree of cellular differentiation based on histological appearance of the tumour.
e.g for breast cancer what are you looking for?
Degree of tubule formation
Extent of nuclear variation
Number of mitosis
Grades: 1 2 3

14. What is the name of the prognostic index in breast cancer?
Nottingham prognostic index:
Size x 0.2
Stage (1 – 3)
Grade (1 – 3)
Score
5-year survival
>/=2.0 to </=2.4
93%
>2.4 to </=3.4
85%
>3.4 to </=5.4
70%
>5.4
50%