1.) TUMOUR VASCULATURE: STRUCTURE AND FUNCTION

Question 1

What are the 2 components that solid tumours are composed of?

Answer 1

• Parenchyma - (tumour cells)

- Stroma - (connective tissue)

Question 2

Explain what the “scirrhous” aspect of a tumour is?

Answer 2

-The hard tumours of the breast.

Question 3

What are tumour cells characterised by?

Answer 3

-Loss of normal tissue organisation applies to the stroma as well as the parenchyma.

Question 4

Rapid stromal growth results in imperfect blood vessel architecture, what does this have implications for?

Answer 4

• Growth of the tumour.

- Response to treatment.

Question 5

What are normal tissues characterised by?

Answer 5

• Contain Linear Blood Vessels
• Lined by Smooth Endothelial Cells with pericytes maintaining vessel integrity of the outside vessel.
• EX matrix of a loose network of collagen and other fibres and contains a few fibroblasts and macrophages.
• Lymph vessels are also present in normal tissues.

Question 6

What are normal tissues characterised by?

Answer 6

• Defective Blood Vessels that are leaky and irregularly shaped with many sac-like formations, dead ends and highly activated endothelia.
• Inefficient Blood Flow
• Blood Vessels are covered by fewer pericytes in normal tissues, causing decreased stability.
• Many tumours lack lymph vessels so intersitial luid and soluble proteins are inefficiently removed.
• EX matrix contains a denser network of collagen fibres which are thicker than in normal tissues.
• Tumour tissue is more rigid than normal loose connective tissue.
• Increased fibroblasts, which binds to collagen fibres in an integrin-dependant manner.
• Increased number of macrophages and other inflammatory cells that release cytokines and GF’s that act on blood vessel and stroma fibroblasts to increase interstitial fluid pressure.
• 02 depleted areas develop which coincide with nutrient and energy deprivation with hostile metabolic micro-environment.

Question 7

What are the three characteristics that capillaries are characterised by?

Answer 7

• Endothelial Cells surrounded by a basement membrane.
• No SMC - (No vasodilation/vasoconstriction)
• Large SA - (exchange of nutrients and gas between blood and tissue).

Question 8

What are the three types of Capillaries?

Answer 8

• Non-Fenestrated
• Fenestrated
• Discontinuous

Question 9

How would a normal capillary be thought of as?

Answer 9

Smooth cylindrical tube w/ pericytes attached to the surface. In capillaries, pericytes are more sparse but still tightly attached to endothelial cells. Unlike tumour cells, pericytes are attached much looser.

Question 10

What is the process of wound healing linked to?

Answer 10

Tumour Associated Angiogenesis, for example, tumours are said to resemble wounded tissues that don’t heal.

Question 11

What two sources do BV in tumours arise from?

Answer 11

• Vessels recruited from pre-existing vasculature

- New Vessels due to an angiogenic response

Question 12

What is the organisation of tumour vasculature dependant on?

Answer 12

• Tumour Type
• Tumour Growth
• Location within the tumour mass

Question 13

There are two types of tumour vascular pattern that can easily be distinguished, what are they?

Answer 13

• Peripheral Vascularisation - (vessels are mainly at the periphery of tumour, the centre is poorly perfused).
• Central Vascularisation - (vessels proliferate from the centre like tree branches)

Question 14

Why are Tumour Blood Vessels leaky and immature?

Answer 14

• Poor recruitment of pericytes and SMC.

- Vessels are multilayered, protrude extension bridging and splitting vessels.

Question 15

What is significant about the Tumour Angiogenesis?

Answer 15

It resembles a physiological response that is initiated but never terminated and is more chaotic.

Question 16

Explain TAM?

Answer 16

• Component of the tumour microenvironment

- 50% of the tumour mass and their prominent role in evasion of immune system.