Neoplasia 3

Question 1

If a solid tumour increases to >2mm diameter, what switch does it need to switch on?
What does this allow?

Answer 1

Angiogenic switch
Pillows tumour to induce and sustain new tumour vasculature

Question 2

Example of angiogenesis-stimulating factor
Example of angiogenesis-inhibiting factor

Answer 2

1. VEGF
2. Thrombospondin

Question 3

Metastasis meaning

Answer 3

Tumour has spread from where they were born to another place (like branches of tree; still in same place but evading more and more places)

Question 4

How do we control angiogenesis levels

Answer 4

Keeping a balance of angiogenesis-stimulating factor and angiogenesis-inhibiting factor

Question 5

Characteristics of Vasculature in normal tissue versus tumour cells

Answer 5

Normal—>
Mature network
Stable
Structure & function of wall appropriate to location

Tumour—>
Dilated, permeable, tortuous (twisty, all over the place) walls
Leaky vessels—> gives rise to perivascular fibrin—> leads to tumour stroma formation
Endothelial cells produce growth factors which stimulate tumour cell growth

Question 6

Why might we get necrosis in a tumour?

Answer 6

-Tumour might be invading blood vessels and rupturing them
-Tumour is growing rapidly

Question 7

Describe the mechanism of invasion of tumour cells

Answer 7

in epithelial cells
Epithelial cells closely adhered to one another. Strong desmosomes hold cells together

Epithelial cell detaches from neighbouring cells;
-desmosomes dismantled
-Catherine function lost
Cell is now isolated
—->
cell transports to new place and attaches very tightly to basement membrane via laminin receptors. Now secretes proteolytic enzymes which degrade the BM and promote invasion into tissue
—->
Basement membrane is degraded
—->
Penetration of BM occurs, cell enters extracellular matrix
Cell changes shape, kind of “slurs” and become more like a mesenchymal/spindle cell in order to get through BM
—->
Now that they are down through BM, local invasion occurs

Question 8

Examples of proteolytic enzymes which help degrade the basement membrane in mechanism of invasion

Answer 8

-type IV collagenase
-plasminogen activator

Question 9

What is the step after local invasion

Answer 9

Metastasis

Question 10

What characteristics do tumours need to invade

Answer 10

Enhanced tumour cell motility
^ protease production
Altered tumour cell adhesion factors

Question 11

First step of being a successful tumour is…

Answer 11

Local invasion

Question 12

Migration of tumour cells is mediated by coordinated changes in what structures?
Stimulated by what?

Answer 12

-cytoskeleton and adhesion structures
-autocrine growth factors (scatter factor) and ECM cleavage product do break down ECM

Question 13

Name the 3 tumour metastasis pathways

Answer 13

Transcoelomic
Haematogenous
Lymphatic

Question 14

Transcoelomic tumour metastasis pathway
-spread through what surfaces
-adv
-examples

Answer 14

Tumour spreads Through thoracic or abdominal surface
-has access to whole of abdomen
-few barriers

E.g mesothelioma, ovarian or pancreatic adenocarcinoma (abdominal tumours), “kissing” metastases

Question 15

Hematogenous tumour pathways
-favoured by what type of cancer

Answer 15

Favoured by sarcomas or mesenchymal

Question 16

Lymphatic tumour pathway
-favoured by what type of cancer

Answer 16

Carcinomas

Question 17

Haematogenous spread
The metastatic cascade - name the steps

Answer 17

1. Clonal expansion
2. Metastatic sub-clone
3. Intravasation
4. Tumour cell embolus
5. Extravasation
6. Metastatic deposit
7. Growth

Question 18

Haematogenous spread:
The metastatic cascade- describe the steps

Answer 18

1. Clonal expansion: Primary tumour undergoes doublings to give different subclones
2. Metastatic sub-clone: transformed successful cancer clone forms and detaches itself from other cells, slurps and penetrates BM
3. Intravasation: after penetrating BM slurs into blood vessel
4. Tumour cell embolus: once in blood vessel can easily spread. One thing that can occur is it can get covered by platelets meaning can travel anywhere; immune system wont recognise is at as a “bad” thing
   Or they are recognised and attacked by host lymphocytes; killed.
5. Extravasastion: if survive travel on and once at suitable site it sticks to endothelial wall and leaves blood vessel into surrounding tissues
6. Metastatic deposit occurs which should now trigger angiogenesis
7. Growth now occurs

Question 19

tumour cells undergo hematogenous spread more often through veins or arteries? Why?

Answer 19

Veins as they are thinner so easier to metastasise through veins

Question 20

Venous routes for tumour cells

Answer 20

Vena Eva
-Heart—> lodge in capillaries particularly lungs portal system—> lodge in liver

Question 21

In the cat Pulmonary adenocarcinoma causes…

Answer 21

Lung digit syndrome in the Cat (spreads to the toes of cat)

Question 22

Way to suppress metastasis/tumour development

Answer 22

1. Upregulate gene encoding Cadherins, which is a gene that the cell needs to break down to unattached from other cells on basement membrane
2. Immunosurveillance

Question 23

Antitumour effector mechanisms are dependent on…

Answer 23

-immune responsiveness of host
-characteristics of tumour

Question 24

Antigen released from dying/live tumour cells is ingested by…

Answer 24

Dendritic cells

Question 25

What do dendritic cells do to released antigen

Answer 25

Fragment it then link to appropriate MHC gene
Activated B or T cells take over its immune response

Question 26

Are dendritic cells part or adaptive or acquired immune response?

Answer 26

Adaptive

Question 27

3 Ways tumours evade immune system

Answer 27

1. tumour cell might have antigen that doesn’t have immune response trigger, antigen hidden from immune system
2. Mutations in MHC genes, right MHC might not be present
3. Tumour itself very clever and produces immunosuppressive products