Name as many hallmarks as you can?
• What happens first:– Genome Instability– Deregulating cellular energetics
• How does it survive (become ‘immortal’):– Self sustaining growth signals– Evade growth suppression– Limitless/endless replication– Avoid immune destruction– Resist cell death– Tumour promoting inflammation
• How does it thrive:– Invasion and metastasis– Angiogenesis
How do cells invade?
• Malignant cells to not adhere as much as normal cells
• Change in the interaction with surrounding stroma
• Produce factors to help spread – increased motility and altered synthesis of enzymes which break down BM and stroma
What is a cadherin?
• Glycoproteins in the cell membrane• Interact between cells and within the cells• Reduced expression and alterations allow cells
to move apart
What are integrins?
• Cell surface glycoproteins• Receptors for different components of the BM• Reduced expression in malignant cells
modifies contact between cell and stroma
What enzymes are involved in BM break down?
• Matrix metalloproteinases• Collagenases• Gelatinases• Stromelysins
What is metastasis?
• Ability of malignant cells to invade into lymphatics, blood vessels and cavities and spread to distant sites
• Not all circulating cells will settle
What are the steps of metastasis?
• Invade BM (MMP/TIMP)• Passage through ECM (MMP/TIMP)• Intravasation (MMP/TIMP/altered integrins)• Immune interaction (↓ MHC Class 1)• Platelet adhesion (GF release)• Adhesion to endothelium/BM (CD44)• Extravasation (integrins/MMP/TIMP)• Angogenesis (angiogenic growth Factors)
What is the difference between primary and secondary metastasis?
• Primary – site where the malignant neoplasm arises
• Secondary – metastasis e.g. carcinoma that has spread to another organ
B-Lymphocytes
• APC present to B-cells in lymph nodes• B cell >> Plasma cells• Produce up to 10 million ab per hour
T-lymphocytes
• Helper cells – regulate• Cytotoxic – destroy infected cells• Viruses and cells transformed by cancer (not
yet adapted to evade immune system)• Need to recognize specific antigen bound to
self-MHC
Immunity and Cancer
• Ag on surface change• Shed ag into circulatory system• Prompt action from cT cells, NK cells and
macrophages• Tumours develop when immune surveillance
breaks down/overwhelmed•
How do cancers become resistant?
• Alteration of drug target• Expression of drug pump• Expression of detoxification mechanisms• Reduced susceptibility to apoptosis• Increased ability to repair DNA damage• Altered proliferation