Lecture 9: Inflammation and cancer Flashcards
What proteins form the junction in the epithelia?
E-Cadherin
What does EMT mean? (wound healing)
Epithelial-to-mesenchymal transition
What is the EMT used for?
EMT occurs at the edge of wounds, enabling
the epithelial cells to migrate and “regenerate”
the damaged epithelium
What is inflammation? (def)
Part of the biological response
of body tissues to harmful stimuli, such as
pathogens, damaged cells, or irritants
Chronic inflammation
functions as a…
…tumor promoter
List of cancers caused by inflammation:
(che pas s’il faut les connaître…)
- Gastric Cancer
- Esophageal Cancer
- Cervical Cancer
- Pancreatic Cancer
- Colorectal Cancer
- Gallbladder Carcinoma
- Hepatocellular Carcinoma
How is Human papilloma virus (HPV), cervical cancer induced?
Two ongenic protein initiate it:
E6: inactivates P53
E7: inactivates pRB
The virus is immunogenic, so infected cells are
generally cleared. But if it’s not the case, it causes chronic inflammation which may induce cancer.
What are NSAIDs?
Non-steroidal anti-inflammatory drugs
What is NFκB and what does it do?
NFκB is a transcription factor that induces cytokines and VEGF, attracting leukocytes and promoting angiogenesis to support tumor growth and inflammation.
What are MDSCs?
Meyloid derived suppressor cells, they are produced in the bone marrow
How do tumours use MDSCs to their advantage?
Tumors release factors that expand MDSCs (using STAT3). They accumulate, suppress T cells, and fail to differentiate into APCs/DCs (denditric cells) in lymph nodes, impairing immune activation
Explain the role of ROS (reactive oxygen species) in bacteria killing by inflammatory cells
Neutrophils and macrophages use NADPH oxidase to make ROS (like superoxide and H₂O₂), which are then converted by myeloperoxidase into HOCl to kill pathogens
Give the 3 mechanisms of immunosuppression by MDSCs
- Use of ROS
- Use of RNOS, peroxynitrite,
can directly inactivate the T-cell
receptor via nitration - Depletion of arginine, which
impairs T-cell function
4 domaines dans lesquels les macrophages ont un role important
1) inflammation
2) tissue homeostasis
3) angiogenesis, tissue remodeling
4) innate immunity
what does TAM stand for?
Tumor-associated macrophages
6 different roles of TAMs to support tumor growth
1) tumor cell invasion
2) inflammation
3) matrix remodeling
4) angiogenesis
5) seeding at distant sites
6) intravasation
what is CSF-1? what happens if it is knocked-out?
-> monocyte/macrophage growth and pro-survival factor
-> reduction of metastasis
what is clodronate? and its role?
biphosphonate that depletes macrophages from tissues
which matrix metalloproteinase (MMP) expressed by macrophages triggers the angiogenic switch?
MMP9, it degrades ECM proteins and stimulates VEGF activation
role of perivascular TAMs
facilitate cancer cell intravasation by enhancing their motility
2 factors that participate in a paracrine loop between cancer cells and TAMs to promote cancer cell invasion
CSF1 released by cancer cell and captured by TAM
EGF released by TAM and captured by cancer cell
what is CCL2? and its role?
-> monocyte chemoattractant protein 1
-> when chronic inflammation, CCL2 promotes attraction of TAMs (expriment CCR2) at primary and metastatic sites
what happens if you block CCL2?
it inhibits metastasis
what are myeloid-derived suppressor cells?
-> tumor-infiltrating myeloid cells which express an immature phenotype
-> they produce ROS and RNOS that abate anti-tumor immunity by blocking T cells
c’est l’IMMUNOSUPPRESSION
