Cancer Stem Cells Flashcards
What are the requirements of cancer stem cells?
Not necessarily multilineage differentiation.
BUT;
- self-renew
- give rise to new tumour with same heterogeneity.
What proportion of cells can give rise to new tumours.
In many tumours only a rare cell type.
In melanomas, 1 in 4 can form tumours.
Staining for MUC1 an shows only few that stain (tumours are heterogeneous).
What is one limitation of an in vivo tumour initiating cell assay?
doesn’t indicate whether tumour promoting cells are responsible for tumour growth within primary tumour.
What is in vivo lineage tracing used for?
to mark where particular cancer types originate.
Showed that prostate cancers with basal and luminal phenotypes can arise from TRANSFORMATION of prostate cells within BASAL LAYER.
What does the transcriptome tell us?
Used to classify breast tumours into different subsets e.g. luminal and basal.
At least 5 different subtypes of breast cancer which express different genes.
Ten new clusters have revealed subgroups with different prognoses (e.g. ER+ve = poor disease-free survival).
Why are quiescent cancer stem cells particularly resistant to therapies?
Low proliferative rate
Overexpress anti-apoptotic proteins such as bcl-2, survivin.
High expression levels of efflux pumping proteins e.g. ABCG2 and MDR1.
What is BM1 and why is it a useful therapeutic target?
overexpressed in most cancer stem cells.
Necessary for self-renewing divisions of adult haematopoietic stem cells.
(2014) - BM1-inhibitor treatment –> reduction in cancer-initiating cell numbers in patient samples and colon cell lines.
