lecture 5- cancer and stem cells Flashcards
what is an oncogene
a gene capable of transforming a normal cell into a tumour cell
what do tumour supressors do
restrict proliferation
what are the 2 groups of kinases involved in the cell cycle
Cdk
cyclins
which part of division is controlled by Cdk1 and cyclin A/B
m phase
which part of the cell cycle is controlled by Cdk 4/6 and cyclin D
G1
which part of the cell cycle is controlled by Cdk2 and cyclin E
G1/S checkpoint
which part of the cell cycle is controlled by Cdk2 and cyclin A
S
what are the 4 main causes of cancer
Chemicals
parasites
radiation
viruses
how is intra-tumour heterogeneity achieved in cancer cells
differences in:
-differentiation state
-proliferation state
-migratory and invasive
-capacity
-size
-therapeutic response
what is the difference between intra and inter tumour heterogeneity
intra- cells within the same tumour
inter-between different tumours
describe the stochastic model for cancer
all tumour cells are equipotent
a proportion of them stochastically proliferate to fuel tumour growth while other tumour cells differentiate
fates are random
describe the cancer cell model
within a tumour, there exists a small subset of cells with stem cell-like properties. These cancer stem cells are the “drivers” of tumour growth, responsible for initiation, maintenance, metastasis, and recurrence of the cancer.
what are the key differences between the stochastic model and the cancer stem cell model
Sto= random cell fate
CSC= predetermined cell fate by stemness
sto= tumour growth driven by random mutations
CSC= tumour growth driven by CSCs
sto= must target all cells
CSC= only need to target CSCs
why can CSCs resist treatment
they have a slow cell cycle
what are to 2 similarities between normal stem cells and cancer stem cells
self renewal
regulated by WNT
what is the difference in differentiation between normal stem cells and cancer stem cells
normal= differentiation for organ functionality
cancer= differentiation for tumour advantage
what are the 2 ways a stem cell can be transformed into a cancer stem cell
1) a specialised cell accumulates mutations which brings it back to its progenitor state
this allows for reprogramming to a cancer cell
2) oncogenic transformation of pre-existing stem cells
what is the in vitro potential of capturing cancer stem cells
establishment of cell lines that can self renew and differentiate
what is the in vivo potential of capturing cancer stem cells
ability to give rise to cancer following transplantation into animals
what is acute myeloid leukaemia
blood cancer affecting the myeloid lineage
how is AML caused
CD34 + and CD38- whihc leads to clonogenic leukaemic progenitors
how can we use stem cells to investigate brain cancer
-dissociate cells
-plate on laminin in presence of cytokines FGF2 and EGF
no expression of undifferentiated markers = differentiation to either glia or neurons
what are the undifferentiated markers of brain cancer stem cells
nestin/Sox2
what are the main approaches of in vitro models of tumourigenesis
xenograft models
cancer cell lines
genetically modified animals
what are the main limitations of in vitro models of tumourigensis
cant capture the transition is a traceable manner
cant track the mechanisms
how can iPSCs / hESCs be used to solve issues with in vitro tumour models
can add the cancer stem cells to the iPSCs and watch the differentiation in human cells
can take hESCs and introduce oncogenic mutations
how are neuroblastomas formed
ectopic overexpression of the transcription factor MYCN in normal neural crest cells
how was it proved that neuroblastomas were cause by overexpression of MYCN
hPSCs were grown with WNT and BMP and they formed neural crest cells
hECS were growth with WNT, BMP, and MYCN overexpression and these formed the neuroblastoma phenotype
