Cancer Flashcards
Why must exactly half of the progeny of a stem cell must stay as a stem cell?
LESS
- Regenerative capacity of the tissue is compromised
MORE
- Cancer?
What is hypertrophy?
Increase in cell size
What is hyperplasia?
Increase in cell NUMBER
When does hyperplasia occur?
- In tissues that can divide
- In tissues with abundant stem cells
What is metaplasia?
- Change in cell differentiation
- Replacement of one MATURE cell type with another MATURE cell type
- Altered differentiation of stem cell
What is dysplasia?
- Changed in cell differentiation
- Replacement of one MATURE cell type with a LESS MATURE cell type
- Disordered
What are the reversible abnormal cellular growth and why?
- Hypertrophy
- Hyperplasia
- Metaplasia
- Dysplasia
Reversible because they are a result of a STIMULUS
What is an irreversible abnormal cellular growth and why?
Neoplasia (resulting from metaplasia –> dysplasia –> neoplasia)
Is a result of an autonomous factor (mutations)
What is cancer?
1) Uncontrolled cell proliferation (eg. mitosis)
2) Aberrant differentitation
- Usually balances with proliferation
3) Uncontrolled cell interaction (invasion and metastasis)
- Not in situ
- Can invade other tissues
4) Cancer cell host interactions
What are 4 cancer cell host interactions?
1) Angiogenesis
- Tumour cells need blood supply
- Hormone dependency
- Hormone production
- Immune response
Tumours are ‘foreign’
What are benign tumours?
- Confined
- Well defined structures
What are the stages in malignant tumour formation?
1) Dysplasia
2) Anaplasia (severe dysplasia)
3) Invasion
4) Metastasis
How do spread (metastasis)?
- Break through the basement membrane
- Into the blood vessels
- Travel to a distant site in the blood vessel
- Fuse with the vessel wall, through the vessel wall
- Colonise distant sites
What are the 4 carcinogenic factors that cause cancer?
1) Chemical
- Smoking
2) Parasites
3) Radiation
- UV
- Ionising radiation
4) Viruses
- insert into the genome
What are the genetic causes of cancer?
- Loss of function in tumor suppressor genes (recessive)
- Gain of function of oncogenes (dominant)
- Need MULTIPLE mutations to initiate neoplasia
Examples of tumor suppressor genes?
Rb
p53
Examples of oncogenes?
myc
ras
abl
What does the stochastic model suggest about cancer?
- Cells have unlimited proliferative capacity
- ALL the cells of a tumour are tumour-initiating so therefore ALL cells can be targets for anti-cancer treatments
- Mutating cells transform growth
- Heterogeneity of cellular composition is limited
What are the problems with the stochastic model?
1) Tumours when treated can recur
2) Tumours are heterogeneous in cellular composition
What do tumours contain?
- Lots of differentiated cells
- High degrees of heterogeneity
In a tumour, where does heterogeneity extend to?
- Differentiation rates
- Proliferation rates
- Migratory and invasive capacity
- Size
- Therapeutic response
What do functional assays show about cancer cells?
- Only a small subset of cancer cells are capable of extensive proliferation
- Only some populations of cells in a tumor can reform tumours in secondary transplantation assays
- Implying there is a hierarchy in a tumours tissue architecture
(only SOME cells are tumour initiating)
What are the implications of tumour heterogeneity?
1) Not every cell in a tumour is the same
- Hard to treat
2) Only some cells n give rise to cells with higher proliferative targets
3) Only SOME cells appear capable of re-initiating the tumours
When treating tumours, what cells do we want to target mostly?
The ‘dormant’ cells which are not highly proliferative but give rise to the highly proliferative cells
What is the ‘cancer stem cell’ model?
Only a small, definable subset of cancer cells are the tumour initiating cells that have the ability to proliferate indefinitely
What does the ‘cancer stem cell’ model suggest?
- Heterogeneity is from differentiation
(A stem cell structure) - Only some cells are targets for anti-cancer treatments as only some cells are tumor initiating
What are ‘cancer stem cells’?
Rare cells within tumours with the ability to self-renew and give rise to the phenotypically diverse tumor cell population
What are the propertires shared between normal stem cells and cancer stem cells?
- Assymetric division
- Regulated by similar pathways
Which cells in the hierachy are cancer stem cells? Why?
Any of the three: - Stem cell - Progenitor cell - Oligolineage precursors Could act as cancer stem cells
- A cancer stem cell is not necessarily derived from a stem cell but it is the ACQUISITION of stem cell PROPERTIES
What cancer stem cell marker is shared between: Colon Lung Liver Pancreas
CD133+
What are the implications of cancer stem cells?
- CSCs may be dormant in G0
- Tumours can grow back after the proliferating cells are removed
How does control of differentiation offer approaches to therapy?
- Deliver something to the tumour which causes differentiation of malignant stem cells to non-malignant derivatives
What are the problems with the CSC model of tumour growth?
1) Testing the CSC model relies of xenotransplantation
- What if the model is not correct because the model is unsuccessful?
2) Testing CSC model often relies upon purification using markers
- Are they shared by other cells?
3) Some tumours loose heterogeneity
- Caused by further mutation and selection
- May evolve intot he stochastic model
