Cells and Immunity
Week 8
Dr Philip Dash
Migration in Cancer
Metastasis;
- Pre-colonization [minutes to hours]; primary tumour creates Local invasion of cells
which connects to blood vessels via intravasation. This tumour releases circulating
tumor cells with platelets attached into the blood.
- Colonization; cells exit blood stream via extravasation, can travels to many sites of
infection;
o Lung capillary wall; tight endothelium
o Brain capillary wall; blood-brain barrier
o Live and bone marrow capillary wall; fenestrated epithelium
- Micro metastasis formation to colonization, which is then clinically detectable
macroscopic metastases. [process can take years]
-
1. Breaking away from primary tumour;
- Cancers are named after tissue of origin and are usually epithelial
o Carcinoma – epithelial tissue [80-90% cancer cases]
o Sarcoma – connective tissue
o Leukemia – bone marrow
o Lymphoma – lymph nodes
- Cell to cell interactions;
o Tight junctions [cells, joined by claudin/occludin joined to actin filaments in
neighboring cells], desmosomes [cadherin -join intermediate filaments of cells
together], gap junctions
o Homophilic interactions; identical molecules join together. cadherins [E-
cadherin join epithelial cells] // Ig-superfamily CAMs [join cells together in
immune system
o Heterophilic interaction; integrin binds to fibronectin [ECM] // Selectins bind
to sugar molecules [on surface of blood vessel cells]
2. Epithelial – mesenchymal transition [EMT]
o Tight junction dissociation [E-cadherin and occluding down regulated], loss of
microvilli
o Adherent junction and desmosome dissociation, loss of apical-basal polarity
o αSMA expression, cytoskeleton reorganization, front-back polarity, migration
o MMP’s up-regulation, basement membrane degradation, invasion
o Epithelial cell markers;
E-cadherin/claudins/occludin/ZO-1/Desmoplakin/cytokeratin’s [molecules
which hold cells together]
o Mesenchymal Markers; N-cadherin, fibronectin, collagen I/III, snail, αSMA,
vimentin
3. Navigating ECM;
Week 8
Dr Philip Dash
Migration in Cancer
Metastasis;
- Pre-colonization [minutes to hours]; primary tumour creates Local invasion of cells
which connects to blood vessels via intravasation. This tumour releases circulating
tumor cells with platelets attached into the blood.
- Colonization; cells exit blood stream via extravasation, can travels to many sites of
infection;
o Lung capillary wall; tight endothelium
o Brain capillary wall; blood-brain barrier
o Live and bone marrow capillary wall; fenestrated epithelium
- Micro metastasis formation to colonization, which is then clinically detectable
macroscopic metastases. [process can take years]
-
1. Breaking away from primary tumour;
- Cancers are named after tissue of origin and are usually epithelial
o Carcinoma – epithelial tissue [80-90% cancer cases]
o Sarcoma – connective tissue
o Leukemia – bone marrow
o Lymphoma – lymph nodes
- Cell to cell interactions;
o Tight junctions [cells, joined by claudin/occludin joined to actin filaments in
neighboring cells], desmosomes [cadherin -join intermediate filaments of cells
together], gap junctions
o Homophilic interactions; identical molecules join together. cadherins [E-
cadherin join epithelial cells] // Ig-superfamily CAMs [join cells together in
immune system
o Heterophilic interaction; integrin binds to fibronectin [ECM] // Selectins bind
to sugar molecules [on surface of blood vessel cells]
2. Epithelial – mesenchymal transition [EMT]
o Tight junction dissociation [E-cadherin and occluding down regulated], loss of
microvilli
o Adherent junction and desmosome dissociation, loss of apical-basal polarity
o αSMA expression, cytoskeleton reorganization, front-back polarity, migration
o MMP’s up-regulation, basement membrane degradation, invasion
o Epithelial cell markers;
E-cadherin/claudins/occludin/ZO-1/Desmoplakin/cytokeratin’s [molecules
which hold cells together]
o Mesenchymal Markers; N-cadherin, fibronectin, collagen I/III, snail, αSMA,
vimentin
3. Navigating ECM;
