07/12/18
Professor Ian Mackenzie
Stem Cells in Cancer
• Genetic predisposition and environment
• Accumulation of mutations
• Stage at diagnosis is key to survival
Epidermal Proliferal Units
• Stem cell in the middle of each skin unit
• Unipotent
• Asymmetric and symmetric division control tumour growth
Tumours
• From murine transplantation (mice)
o Showed stem cells exist in tumours still
o Cancer initiating cells are homologous to stem cells
• Human skin cells have different growth patterns
o Tight = cancer
o Loose = stem cells
o Other = skin cells
• Holoclone – the original cancer cell
• Paraclone – stem cell in a tumour
• In lab you can stain and visually see different cells within the cancer
Therapeutic Resistance
• Stem cells are 10 times more resistant than cancer cells and often survive radiation
• Usually only kill some, so some are left for recurrence
• Stem cells cause tumour recurrence
Metastasis
• Skin is very tightly packed, so tumours will be too
• Changes in epithelial to mesenchymal cell (EMT)
o Lose keratin, cadherin and cell adhesion
o Necessary in wound healing
o Cancer hijacks this to spread
• So, by this change they can spread
• Motile amoeboid CD44 cells spread
• Can go back and forward genetically and induce
o Only found in melanomas
Clinical
• Pathologists don’t see EMT cells in tissue specimens but do in the lab
• Could not be visible?
Professor Ian Mackenzie
Stem Cells in Cancer
• Genetic predisposition and environment
• Accumulation of mutations
• Stage at diagnosis is key to survival
Epidermal Proliferal Units
• Stem cell in the middle of each skin unit
• Unipotent
• Asymmetric and symmetric division control tumour growth
Tumours
• From murine transplantation (mice)
o Showed stem cells exist in tumours still
o Cancer initiating cells are homologous to stem cells
• Human skin cells have different growth patterns
o Tight = cancer
o Loose = stem cells
o Other = skin cells
• Holoclone – the original cancer cell
• Paraclone – stem cell in a tumour
• In lab you can stain and visually see different cells within the cancer
Therapeutic Resistance
• Stem cells are 10 times more resistant than cancer cells and often survive radiation
• Usually only kill some, so some are left for recurrence
• Stem cells cause tumour recurrence
Metastasis
• Skin is very tightly packed, so tumours will be too
• Changes in epithelial to mesenchymal cell (EMT)
o Lose keratin, cadherin and cell adhesion
o Necessary in wound healing
o Cancer hijacks this to spread
• So, by this change they can spread
• Motile amoeboid CD44 cells spread
• Can go back and forward genetically and induce
o Only found in melanomas
Clinical
• Pathologists don’t see EMT cells in tissue specimens but do in the lab
• Could not be visible?
