L03-Tumour Biology

Question 1

What is metastasis?

Answer 1

The movement of a cancer from its tissue of origin to some other part of the body that is not its origin.

Question 2

What is invasion in terms of cancer cells?

Answer 2

the movement of cancer malignant cells to new environments where they should not be.

Question 3

How do tumour cells move to other organs?

Answer 3

They undergo epithelial mesenchymal transition (happens normally during wound healing) which helps them leave the primary site. They then move in the circulatory system until they find tissues with the right kind of receptors where they will extravasate.

Question 4

What changes must occur in tumour cells to make them malignant?

Answer 4

Genetic changes to oncogenes or lack of tumour suppressor genes. Epigenetic changes that lead to over or under expression.

Question 5

What are some of the growth factors that help with tumour genesis?

Answer 5

Colony stimulating factor (CSF, brings macrophages)
EGF (Epidermal growth factor) secreted by macrophages
Il6 from adipocytes prime tumours to be malignant.

Question 6

How do cancer cells break away from the primary tumour?

Answer 6

There can be a mutation in the B-catenin protein that binds the cells together with Cadherins. When this beta-catenin is mutated it can release from the cadherins causing the cells to no longer attach to one another. This also releases beta-catenin into the cell where it is normally degraded by a complex binding to it.

Question 7

What happens in cells where breakdown of beta-catenin does not occur?

Answer 7

APC-tumour supressor gene is required for degradation of beta catenin and without this it isnt broken down. The beta catenin if not broken down promotes the transcription of oncogenes which induces proliferation of the cancer cells.

Question 8

What enzymes are required for tissue invasion?

Answer 8

Degrading enzymes are released called matrix metalloproteinases which degrade the matrix. This is done by stromal cells in the micro-environment rather than the cancer cells.

Question 9

What are the consequences of tumour vascularisation?

Answer 9

Cancer cells are extremely metabolically active so need O2, glucose and metabolites. They also excrete toxic metabolites into the bloodstream. Since these vessels are generated very quickly they are dilated and have large pores.

Question 10

Why do cancers induce angiogenesis?

Answer 10

Hypoxia drives angiogenesis so the hypoxia created by cancers drives angiogenesis. The metabolites from the cancer cells causes activation of transcription of HIF (hypoxia induced factor) which causes cancer cells to switch to glycolysis. The HIF also promotes pro-angiogenic factors such as angiopoetin 2.

Question 11

What do malignant cancer cells not exhibit that benign cells do exhibit?

Answer 11

Malignant cells do not exhibit density dependent inhibition of growth. This means that when the cells form a complete continuous layer they do not stop growing like benign cells do.

Question 12

What are the four main characteristics of malignant tumours?

Answer 12

Malignant cell growth
Metastasis
Glycolytic switch
Angiogenic switch

Question 13

Why are tumours often hard lumps?

Answer 13

Due to the collagen secreted by cells in the tumour stroma.

Question 14

What percentage of the tumour is made up of tumour cells?

Answer 14

Only 30-40% as the stroma makes up the rest that is the micro environment.

Question 15

What is the main trascription factor that regulates epithelial mesenchymal transition?

Answer 15

SLUG

Question 16

What do these four factors mean? and are characteristic of?
Density dependent inhibition of growth
Contact inhibition of movement
Anchorage dependence
Adhesion

Answer 16

They are characteristic of malignant cells. This is because malignant cells dont stop growing when they become too dense or are in contact with one another. They are not dependent on a basement membrane to grow or anchorage to one another.

Question 17

Why do cancer cells undergo glycolytic swtich?

Answer 17

As cells in the centre of the tumour do not recieve enough oygen and glycolytic switch is induced by hypoxia. This is not as good as aerobic respiration but is essential for the cancer cells to survive. Often outcompete surrounding cells for glucose.

Question 18

How can you test for cancers using their increased glucose uptake?

Answer 18

Using flourescent glucose compounds that will show up on PET scans.