20.11.19
L6 – Cancer (cell adhesion and cell migration)
Keywords:
Metastasis (dispersal of cancer around the body), intravasation,
Lecture:
Metastasis
o 90% of patients die bc metastasis
o 4 most common sites of metastasis (via circulation)
Bone, liver, lungs and brain
o Steps
Primary tumor (abnormal local growth)
Local invasion (spread though ECM)
Intravasation (moves into blood stream and circulate)
Arrest at organ and extravasation occurs (out of blood stream)
Micro metastasis formation to metastatic colonization
o Radiotherapy and surgery ineffective when metastasis
o Immunotherapy and chemotherapy have to be used
Cancer types
o Carcinoma – epithelial tissue (90%)
o Sarcoma – connective tissue
o Leukemia – bone marrow
o Lymphoma – lymph nodes
Cell-cell interactions
o Tight junctions – link actin
o Desmosomes – interfilaments
Homophilic interactions (same filaments on both cells) eg Cadherins
Heterophilic interactions (different filaments on both cells) eg integrins
(migration), selectins (immune cells)
o Barrier for cancer cells (broken links in metastasis)
EMT (epithelial mesenchymal transition)
o Cancer cells lose epithelial markers
Connections detached (eg claudins/occludins and e-cadherin)
Lose polarity/microvilli
ECM
o Fibroblasts remodel via collagen/cytokinin’s
o Cancer cells require to
Change integrin molecules (pull self forward in ECM/move into blood
vessels)
Learn how to degrade ECM (MMP enzymes required – expressed/secreted
as proenzymes)
Enzymes regulated by TIMPs by fibroblasts
o TIMPs inhib MMPs (downregulated cancer) decreasing ECM
degradation
Forces/immune cells = blood is hostile
↑ interactions w/platelets (pretend have an injury) to form a barrier around
the platelets
L6 – Cancer (cell adhesion and cell migration)
Keywords:
Metastasis (dispersal of cancer around the body), intravasation,
Lecture:
Metastasis
o 90% of patients die bc metastasis
o 4 most common sites of metastasis (via circulation)
Bone, liver, lungs and brain
o Steps
Primary tumor (abnormal local growth)
Local invasion (spread though ECM)
Intravasation (moves into blood stream and circulate)
Arrest at organ and extravasation occurs (out of blood stream)
Micro metastasis formation to metastatic colonization
o Radiotherapy and surgery ineffective when metastasis
o Immunotherapy and chemotherapy have to be used
Cancer types
o Carcinoma – epithelial tissue (90%)
o Sarcoma – connective tissue
o Leukemia – bone marrow
o Lymphoma – lymph nodes
Cell-cell interactions
o Tight junctions – link actin
o Desmosomes – interfilaments
Homophilic interactions (same filaments on both cells) eg Cadherins
Heterophilic interactions (different filaments on both cells) eg integrins
(migration), selectins (immune cells)
o Barrier for cancer cells (broken links in metastasis)
EMT (epithelial mesenchymal transition)
o Cancer cells lose epithelial markers
Connections detached (eg claudins/occludins and e-cadherin)
Lose polarity/microvilli
ECM
o Fibroblasts remodel via collagen/cytokinin’s
o Cancer cells require to
Change integrin molecules (pull self forward in ECM/move into blood
vessels)
Learn how to degrade ECM (MMP enzymes required – expressed/secreted
as proenzymes)
Enzymes regulated by TIMPs by fibroblasts
o TIMPs inhib MMPs (downregulated cancer) decreasing ECM
degradation
Forces/immune cells = blood is hostile
↑ interactions w/platelets (pretend have an injury) to form a barrier around
the platelets
