Biology of Cancer & Metastasis Stem Cells

How did they determine cancer arises from one transformed initiating clone

by showing that a single mouse leukemic cell can seed and form a new tumour in a healthy mouse

Difference between differentiated and non-differentiated cells in forming tumours

differentiated cells can no longer form tumours in secondary recipitents

Properties of normal adult stem cells

maintain and regenerate tissues during homeostasis

What is the classical concept of cancer stem cells

The cancer stem cell hypothesis posits that CSCs are responsible for maintaining tumour hetergeneity, duelin tumour growth and therapy resistance

functional traits of cancer stem cells

1. generate all cell types present in a tumour

2. self-renew and generate non-CSC progeney

3. found in many cancers

4. unlimited self-renewal potential

5. slow cycling dormant clones have highest resistance to chemo

how are new CSC clones acquired

mutations or niche effect (environment allows cells to change) → advanced stage hit with chemo → relapse with new dominant clone

what is the flattening of CSC hierarchy at late stages

mutation or niche effect → advanced stage → competition and dominace by CSC clones

How are CSC functional traits sustained

tumour microenvironment compose of immune cells, stromal cells and ECM

examples of CSC Niches (3)

1. vascular endothelial cells

2. Hypoxia

3. Inflammatory cells and molecules

Goal in identifying CSC biomarkers

look for types specific to different cancers because highly sensitive and specific markers for CSCs remain elusive

examples of metastasis-initiating clones within CSC populations

1. CD44+ breast cancer cells enriched in metastatic activities

2. CD44+CXCR4+ pancreatic CSC cells in invasion and metastasis

3. CD26 and CD133 in colorectal

What are the six mechainsms being targeted by CSC-based therapeutics

1. targeting cell surface markers of CSCs

2. targetin CSC signalling pathways

3. microRNA-based therapeutics

4. targeting components of tumour microenvironments

5. targeting CSC metabolisms

6. immunotherapy