Cancer stem cells Flashcards
a cell is classified as a stem cell when is satisifes what three criteria?
- Undifferentiated or unspecified.
- Have the ability to self-renew.
- Mature and differentiate
what are transiently amplfying cells?
transit amplifying cells
an undifferentiated population in transition between SCs and differentiated cells
a gradient of what three signals fine tune the differentiation pattern in the intesinal crypt?
Wnt on the proliferation end (crypt) (promoting self renewal capacity of SCs)
BMP and TGFbeta on the differentiation end
what three pathways involved in self renewal are deregulated in cancer cells?
- Wnt
- Shh (sonic hedgehog)
- Notch
give the 6 hallmarks of cancer
- Sustained proliferation
- Invasion
- Metastasis
- Replicative immortality
- Ability to evade growth suppression and apoptosis
- Heterogeneity
how does tumour heterogeneity begin?
wiht one single cell that undergoes genetic or epigenetic alterations
tumour heterogeneity is responsible for what features of cancer
tumour progression, metastasis, resistance to therapy and relapse
what is intratumoural hetergeneity?
heterogeneous expression of different markers among cancer cells
distinct tumor cell populations (with different molecular and phenotypical profiles) within the same tumor specimen
what is intertumoural heterogeneity?
heterogeneity among the tumours arising in different patients with a given cancer
give three mechanisms influencing tumour heterogeneity
- Genomic landscape of individual tumours and their clonal evolution
- Existence of different populations of cancer cells with cancer stem cells (CSCs) residing at the top of the hierarchy
- Tumour microenvironment
give three mechanisms influencing tumour heterogeneity
- Genomic landscape of individual tumours and their clonal evolution
- Existence of different populations of cancer cells with cancer stem cells (CSCs) residing at the top of the hierarchy
- Tumour microenvironment
tumour evolution is affected by what factors
exposure
constituative genetics
systemic regulators (hormones, growth factors, immune/inflammatory response)
local regulators (oxygen metabolism, nutrients, cell-cell/ cell stroma/matrix, space)
architectural constraints (physical compartments, basement membranes, restricted niches)
what is the process by which tumours evolve?
a darwinan process whereby additional somatic mutations confer selective advantages to more fit clones
tumour evolution following the darwinan process is similar to What normal cellular process
similarr to the way stem cells produce transit amplying cells and differentiated cells
why are stem cells the focus of this new cancer stem cell theory?
only stem cells have the ability to self-renew - neoplasia is essentially dysregulated self renewal
stem cells are long lived cells which can acquire the necessay number of sequential mutations to convert a normal cell into a malignant one
what is the origin of the theory of cancer stem cells?
in 1997 Dominique Bonnet discovered an organised hierarchy in human acute myeloid leukemia that originated from primitive hematopoietic cells
what key cell markers are present on long term hematopoietic stem cells but not on its progenitors?
LT-HSCs express CD34+ but are devoid of CD38-
progenitors dont have CD34-
can be Cd34- CD38+ and CD34- CD38-
how did Bonnet discover the leukemic stem cells in human acute myeloid leukemia?
both stem cells (CD34+/Cd38-) and transient amplifying cells (CD34+/CD38+) were injected into mice however only one group of cells resulted in leukemia, the stem cells
isolation of cell types in this mouse found all the intermediate progenitors and mature cells - all lineages - of hematopoeisis in the tumour
Identification of human breast cancer stem cells requires what cell markers
CD44+/CD24-
higher fraction of CD44+/CD24- cells in breast cancer is associated with what three things
- shorter disease free interval
- shorter overall survival
- greater incidence of metastasis
only a fraction of breast cancer cells present the capacity to reform secondary tumours following their transplantation into immunodificient mice, what markers do they possess
CD44+/ CD24-
only leukemic cells expressing the same markers as ________________ were leukemia initiating cells: _________________
hematopoietic stem cells (HSCs: Cd34+CD38-)
leukemic stem cells (LSCs)
what is another name for tumour propagating cells
cancer stem cells