Metastasis

Question 1

What are metastases formed by?

Answer 1

By cancer cells that have left the primary tumour and traveled vi blood/ lymphatic vessels

Question 2

What % of cancer deaths are caused by mestastasise?

Answer 2

90%

Question 3

What is the linear progression model?

Answer 3

During local progression aggressive cells and selected and dissemination initiates.
-The metastatic sites are then sequentially seeded.

Question 4

What is the parallel progression model?

Answer 4

• Involves early dissemination (1-4mmm)

- Different organs are seeded in parallel not sequentially (unlike linear)

Question 5

What is the metastasis cascade?

Answer 5

• Primary tumour forms
• Local invasion
• Intravasation
• Transport through circulation
• Arrest in microvessles of various organs
• Extravasation
• Formation of a mcirometastasis
• Colonization - formation of a macrometastasis

Question 6

Briefly describe the EMT process

Answer 6

• EPithelial cells stop expressing E-Cadherin and start expressing mesenchymal markers such as vimentin. This allows them to leave the tissue and enter the stroma.
• Process is stimulated by factors secreted by the stroma such as TGFb and TNFa

Question 7

What is intravasation of cancer cells stimulated by?

Answer 7

TAM (tumour associated macrophages)

Question 8

How do cancer cell emboli protect themselves from the hostile environemtn of the blood vessel?

Answer 8

By either clumping together or by using immune cells to protect them. (the cancer cells are taken up by immune cells so they cant be broken apart)

Question 9

What are the 2 methods of extravasation?

Answer 9

Rapid and slow
Rapid= trigger endothelial cell of vessel wall to retract, creating space for the cancer cell to extravasate.
Slow= takes days, requires proliferation and subsequent destruction of parenchyma.
(Not all tumour cells can extravasate like immune cells so they have to do it the slow way)

Question 10

What size is a macrometastasis?

Answer 10

2mm or more

Question 11

What are the different metastases pathways?

Answer 11

• Transcoelomic (cancers that arise on surface of abdominal/ thoracic structures)
• Lymphatic
• Haematogenous (sarcomas)

Question 12

What does metastatic tropism mean?

Answer 12

Their preference to spread to a certain tissue

-Depends on the ability of a tumour cell to adapt to the microenvironment and layout of circulation.

Question 13

Describe bone metastases

Answer 13

• Arrive at bone via marrow vessels
• Adhere to specialised stromal cells coating bone facing the marrow
• Attracted by growth factors expressed by ECM
• Cancer cells activate osteoblasts/ osteoclasts at different extents so you can have osteolytic and osteoblastic metastases.

Question 14

What is involved in the detection of metastases?

Answer 14

• Physical examination

- Diagnostic imaging

Question 15

Describe the use of thoracic radiography and metastases detection

Answer 15

• Used to find tumour spread via the haematogenous route
• osteosarcoma, melanoma, haemangosarcoma , mammary tumours
• not sensitive and easily miss small ones
• Left and right lat views and DV views needed

Question 16

Describe the use of ultrasonography and the detection of metastases

Answer 16

• Sensitive detection method for lesion in liver, spleen and kidneys
• Limited use for determining nature of lesion
• Guided biopsy helpful

Question 17

What are the implications for treatment if metastases have been found?

Answer 17

Surgical procedure MUST be followed by systematic therapy of chemo and/ or radiography.