Cancer Invasion and Metastasis Flashcards
When is a tumour considered to be benign?
If the neoplastic cells are clustered in a single mass
When is a tumour considered to be malignant?
Once the tumour has undergone metastasis
How many different types of tumours are there?
As many as there are different types of human cells - 200
What does the grouping of a tumour depend on?
The tissue of origin
There is increasing use of molecular definitions to stratify cancers
What are benign tumours of epithelial tissues called?
- Adenomas
- Papillomas
What are malignant tumours of epithelial cells called?
Carcinomas
What are benign connective tissue tumours called?
- Lipomas
- Fibromas
- Haemangiomas
What are malignant tumours of connective tissue called?
Sarcoma
What are benign tumours of lymphoid tissue called?
Lymphoid hyperplasia
What are malignant tumours of lymphoid tissue called?
Lymphoma
What are malignant tumours of haemopoietic tissues called?
Myeloid proliferations
What are malignant tumours of haemopoietic cells called?
Leukaemia
What are benign tumours of germ cells called?
Teratomas
What are malignant tumours of germ cells called?
Germinoma
Which of the hallmarks of cancer relate to metastasis?
- Induction of angiogenesis
- Activating invasion and metastasis
What can be determined about tumour metastasis from studies of colon carciogenesis?
Cancer is a multi-hit disease, with accumulation of genetic changes, and the transition to metastasis occurs at the end, once a lot of damage has already been done
What are the steps in the formation of a metastasise?
- Primary tumour formation
- Localised invasion
- Intravasation
- Transport through circulation
- Arrest in microvessels of various organs
- Extravasation
- Formation of micrometastasis
- Colonisation and formation of macrometasis
What allows localised invasion of a tumour?
Formation of blood vessels
What happens in tumour intravasation?
Interaction of tumour with platelets, lymphocytes, and other blood components
What must be done at all stages of metastasis?
Evasion of the immune system
What allows metastasis to be successful despite it being an inefficient process?
Sheer force of numbers - there are potentially millions of cells circulating
What % of disseminated tumour cells survive to be solitary cells in a secondary organ?
80%
What are the potential fates for solitary cells that get into a secondary organ?
- Proliferate
- Viable but dormant
- Die
What % of disseminated tumour cells initiate growth into micrometastases?
2%
What % of disseminated tumour cells persist to grow into macrometastases?
0.02%
Give an example of where other types of cells in the microenvironment are involved in metastasis
Tumour associated macrophages promote breast cancer metastasis
How are macrophages involved in breast cancer metastasis?
A paracrine loop between tumour cells and macrophages is required for tumour cell migration in mammary tumours
Describe the paracrine loop between tumour cells and macrophages required for cell migration in mammary tumours
Tumour cells express CSF-1, which binds to CSF-1 receptor on macrophages and allows them to proliferative and survive. Macrophages express EGF, which binds EGF-receptors on tumour cells
Why is the loss of cell to cell adhesion important in tumour cell metastasis?
Epithelial cells are very tightly organised with strong cell-cell adhesion, which has to be detatched in order for cells to move
What are the different types of adhesions that join cells?
- Tight junction
- Adherens junction
- Desmosome
What are cadherins?
Key adherence molecules that span the plasma membranes of cells, and allows attachment of 1 cadherin to another
What is cadherin adhesion regulated by?
Calcium
Give an example of a cancer where E-cadherin expression is important
Abberrant or absent E-cadherin expression is associated with aggressive bladder cancer
What other features of cancers is aberrant or E-cadherin expression associated with?
- Advanced tumour stage
- Tumour de-differentiation
- Lymph node metastasis
How is epithelial to mesenchymal transition activated?
Different signalling pathways; STAT3 pathway, FGF pathway, ER pathway, TGFß pathway
Broadly, how do signalling pathways activate epthelial to mesenchymal transition
The signalling molecule induces the expression of key transcription factors - Twist, Snail, SIP1. These transcription factors suppress E-cadherin expression, and increase mesenchymal markers
What are the categories of migration mechanisms?
- Collective
- Individual
What are collective migration mechanisms mainly linked to?
Loss of E-cadherin expression
What migration strategies are employed in collecting migration?
- Multicellular strands/sheets
- Cluster/cohorts
Give two examples of tumours that migrate in clusters/cohorts
- Epithelial cancer
- Melanoma
Give two examples of tumours that migrate in multicellular strands/sheets
- Epithelial cancer
- Vascular tumours
What are individual migration mechanisms predominantly associated with?
Integrin mechanisms and secretions of proteases
What migration strategies are employed by the individual migration method?
- Ameoboid
- Mesenchymal (single cells)
- Mesenchymal (chains)
Give three tumour types that migrate by the ameoboid strategy
- Lymphoma
- Leukaemia
- SCLC
Give three tumour types that migrate by the mesenchymal mechanism
- Fibrosarcoma
- Glioblastoma
- Anaplastic tumours
What are the steps in mesenchymal migration?
- Protrusion
- Adhesion
- Translocation
- Retraction
What is the protrusion stage of mesenchymal migration associated with?
Key enzymes at the leading edge
What are focal adhesions?
Key complexes of proteins that allow attachment of cells to the extracellular matrix
What is vinculin?
A component of focal adhesions that act as specific attachment pads
What do integrins consist of?
- Transmembrane receptors
- 24 heterodimers - 18 alpha and 8 beta subunits
What does the ECM consist of?
- Mesh of fibrous proteins - laminins, collagens, fibronectin, elastin
- Glycosaminoglycasns
