Tumour growth and development

Question 1

Carcinoma

Answer 1

Cancer derived from epithelial cells

80% of cancers

Question 2

Sarcoma

Answer 2

Cancer derived from connective tissue

Question 3

Cancer genetic instability

Answer 3

Cancer cells have multiple/loss of whole chromosomes and chromosomal rearrangements

Question 4

Colorectal cancer progression

Answer 4

A model of multi-step carcinogenesis
Loss of APC (TSG) leads to hyperplastic epithelium
Accumulation of additional mutations leads to adenoma (activation of k-ras, loss of 18q TSG)
Loss of p53 leads to carcinoma

Question 5

Angiogenesis

Answer 5

Tumour growth limited by distance oxygen can diffuse
Pericytes loosen and blood vessel dilates
New vessels bud off and detect areas of hypoxia (angiogenic sprouting)
New vessel formation and maturation

Question 6

Angiogenesis activators

Answer 6

Typically receptor tyrosine kinase ligands such as vascular endothelial growth factors (VEGF-A, B, C)
Can be fibroblast growth factors (FGF1,2)

Question 7

Metastasis

Answer 7

Escape of cancer cells from primary site and establishment in a secondary site
Responsible for 90% of cancer mortality

Question 8

Basement membrane

Answer 8

Acellular structure that separates epithelial cells from underlying tissue (stroma)

Epithelial cells attached to each other via E-cadherin

Question 9

Local invasion

Answer 9

Tumour cells or adjacent stroma secretes proteases (matrix metalloproteases)

Allows cells to breach basement membrane and invade local stroma

Question 10

Epithelial to mesenchymal transition

Answer 10

Expression of TFs (Twist, SNAI1, SNAI2)
Allows cells to become motile and invasive
Adopt fibroblastic phenotype and become more apoptosis resistant
Repress E-cadherin and upregulate N-cadherin (weaker)

Question 11

Intravasation

Answer 11

Cancer cells interact with platelets and lymphocytes, forming microthrombi which may partially protect them

Cells may die through anoikis or hyrdrodynamic stress while transporting through circulation

Question 12

Arrest and extravasation

Answer 12

Cells lodged in microvessel and then extravasate
Cells begin to proliferate at new site (micrometastasis)
Mesenchymal to epithelial transition

Question 13

Colonisation

Answer 13

Least efficient step in metastasis as new tissue likely has different growth and survival factors

Some tissues offer a more friendly environment

Question 14

Common sites of metastasis

Answer 14

Prostate and breast to bone marrow
Pancreas and colon to liver

Partly due to path of circulation

Question 15

Premetastatic niches

Answer 15

Specialised microenvironment with accumulation of aberrant immune cells and extracellular matrix proteins in target organs
Promote tumour cell colonisation and growth in the secondary organ
Primary tumour may produce exosomes involved in creation of niches