HC14 - Cancer stem cells Flashcards
total surface area intestine
30-40 m2
renewal intestine
~7 days = 10^12 cells
colorectal cancer (CRC)
second most common cancer > APC mutation
niche cells
Paneth and mesenchymal cells
niche signals
Wnt, Notch, EGF, ECM
identifying stem cells
lineage tracing with markers
intestinal stem cell niche
dominant factor that drives regeneration
colorectal tumorigenesis
APC mutation > fast growing crypts
intra-tumor heterogeneity (3)
- multi-lineage differentiation
- non-malignant cells = micro-environment
- immune cells
first evidence cancer stem cells in a solid breast malignancy
200 CSCs form a tumor in a NODSCID mouse > CD44+
glioblastoma marker
CD133+
colon cancer marker
CD133+
cancer stem cells characterisitcs (3)
- high Wnt activity
- multi-lineage differentiation capacity
- self-renewal
mechanisms of CSC resistance (4)
- express high levels of anti-apoptotic proteins
- primed to respond to DNA damage
- protected by the niche
- express high levels of drug transporters
patient prognosis
worse with CSC signature > TOP-GFP = high