Lecture notes Cells and Immunity Cancer and NO (BI2BC45)

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