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Cancer Part 2 (Invasion and Metastasis (Proteases (Gelatinases: degrade…
Cancer Part 2
Invasion and Metastasis
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Neoplasm invades basement membrane by releasing proteases and tumour cell motility. Neoplasm also has decreased cell-cell adhesion so they can escape
A cancer cell grows to form a neoplasm in situ. This neoplasm then becomes invasive when it breaks through the basement membrane of the host cell and enters the extracellular matrix
Proteases
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Interstitial collagenases: degrade types I, II, III collagen
METASTASIS: The process whereby malignant tumours spread from their site of origin to form other tumours at distant sites
Steps of metastasis:
- Detachment of tumour cells
- Invasion of surrounding connective tissue to reach blood + lymphatic vessels
- Intravasation into lumen of vessels
- Evasion of host defence e.g. NK cells
- Adherence to endothelium at new location
- Extravasation from vessel lumen into surrounding tissue
Tumours which commonly metastasise to bone: prostate, breast, thyroid, lung, kidney
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Tumours which commonly metastasise to liver: colon, stomach, pancreas, intestine (as these organs connect to the liver via the hepatic portal vein)
Angiogenesis
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Angiogenesis inhibitors: angiostatin, endostatin, vasculostatin
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Tumour Immunology
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Tumour Associated Antigens (TAA) = Antigens on tumours and normal cells but they are over expressed in cancer cells
Characteristics of cancer:
Evades apoptosis
Limitless replication
Invades tissue
Escapes immune surveillance
Sustained angiogenesis
Ignores anti-proliferative signals
Cancer immunosurveillance: immune system can recognise and destroy newly transformed neoplastic cells
Cancer immunoediting: Tumours are genetically unstable. Immune system can kill and induce changes in the tumour
Evidence for tumour immunity:
Spontaneous regression
Regression of metastases after removal of primary tumour
Infiltration of tumours by lymphocytes + macrophages
Lymphocyte proliferation when draining lymph nodes
Higher incidence of cancer in immunosuppressed people
Evidence for tumour escape:
Tumours change so that they are not detected
Tumours promote immune suppressor cells to evade immune system
Cells involved in immune response to tumours: T-cells, antibodies, NK cells, macrophages
Immunotherapy
Active
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Vaccination via killed tumour, viral vectors or purified tumour antigens
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Carcinogenesis
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RB1 is a transcriptional regular gene. In deletions, retinoblastomas form - malignant tumours of the retina
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Oncogenes: Genes driving the neoplastic behaviour of cells. They are activated by mutations e.g. point mutation, translocation, amplification
Screening
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Overdiagnosis bias: Diagnosis of lesions that are histologically malignant but are clinically harmless
Lead time bias: Earlier detection does not effect the inevitable fatal outcome, but prolongs survival time
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UK has screening programmes for cervical, breast and colorectal cancer
Microenvironment
Tumour Hypoxia = Blood supply cannot provide enough oxygen for tumour cells. Tumour cells adapt to low oxygen
Problems with tumour hypoxia:
Stimulates new vessel growth to deliver more blood to tumour
Suppresses immune system, as it cannot function in hypoxia
Resistant to radiotherapy + chemotherapy
Increased tumour hypoxia after therapy
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Mutations
Germline
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E.g. BRCA1 +2, MAGE-1, MAGE-3
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