L03 Tumour biology Flashcards
What are the 4 characteristics of malignant tumours?
Malignant cell growth
Metastasis
Glycolytic switch
Angiogenic switch
Malignancy is associated with the loss of….
- DENSITY DEPENDENT INHIBITION OF GROWTH; cancer cells keep growing
- CONTACT INHIBITION OF MOVEMENT; do not move away from each other when they touch
- ANCHORAGE DEPENDENCE; malignant cells do not need contact with a substratum
- ADHESION; cancer cells adhesion to each other is dysregulated
What do benign tumours exhibit?
Density-dependent inhibition of growth (malignant cells do not exhibit this)
What is metastasis?
Tumour implant discontinuous with the primary tumour
Describe the process of metastastis.
- invade beyond normal tissue boundaries
- detach from primary tumour mass
- enter vascular or lymphatic vessels
- adhere to endothelium and exit from circulation
- local tissue invasion and induction of angiogenesis
What is the role of epithelial-mesenchyme transition in metastasis?
Enables tumours to migrate through tissues, then they can use MET to revert back to epithelial tissue
How is EMT regulated?
Transcription factors; a decrease in epithelial markers and cell adhesion molecules, and an increase in mesenchymal markers
Examples of epithelial markers?
E-cadherin
Occludins
Claudins
Examples of mesenchymal markers?
N-cadherin
Vimentin
Fibronectin
What are the 4 key properties of a metastatic cell?
- Detachment from primary mass
- Invade ECM
- Adhesion to endothelium, extravasation
- Colonisation of and survival in secondary organ
How does a metastatic cell detach from the primary mass?
Downregulated CAMs e.g. E-cadherins
What is the role of Beta-catenin in tumourigenesis?
E-cadherins are linked to the actin cytoskeleton through catenins. The APC protein phosphorylates the free Beta-catenin. When the APC gene is mutated, Beta-catenin accumulates and binds to TCF/LEF family and translocates to the nucleus. Switches on c-myc gene, leads to division.
How do metastatic cells invade the ECM?
Activated stroma secrete MMPs which allow the tumour cells to invade the tissue by degrading the ECM
How do metastasising tumour cells adhere to the endothelium?
Selectins on endothelial cells bind to integrins on tumour cells
What and why is the preferred method of respiration by tumour cells?
Glycolysis
It is fast, does not require oxygen, and enables tumour cells to outcompete normal cells for scarce glucose supply.
