cancer: metastasis
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Cancer: Metastasis. By Joshua Bower and Asfand Baig Peer Support 2013/2014. Define metastasis. Ability of malignant cells to invade and spread to distant (non-contiguous) sites. Distinguish between a primary and secondary tumour. Primary - site where the malignant neoplasm arises - PowerPoint PPT PresentationTRANSCRIPT
Cancer: MetastasisBy Joshua Bower and Asfand Baig
Peer Support 2013/2014
Define metastasis
• Ability of malignant cells to invade and spread to distant (non-contiguous) sites
Distinguish between a primary and secondary
tumour
• Primary - site where the malignant neoplasm arises
• Secondary - the site where the initial neoplasm has metastasised to
By what routes do cancers spread? [4]
• Locally
• Haematogenously (in the blood)
• Via lymphatics
• Transcoelomically (across a cavity; peritoneum or pleura)
Where do tumours of lymph node cells sit?
• In the subcapsular sinus - a region with few lymphocytes, thus permitting free lymph flow
List FOUR common sites for cancer metastasis [4]
• Brain
• Bone
• Lung
• Liver
Give THREE examples of primary tumours which commonly
metastasise
• Prostate
• Breast
• Lung
Problem based learning! PBL
A patient with known prostate cancer presents with paralysis of his legs.
What is your diagnosis?
• Spinal cord compression
• Cancer cells have metastasised to the spinal cord and the tumour is compressing the nerves
• The prostatic venous plexus connects with vertebral veins, which is why it commonly spreads to the spinal cord
Describe the 8 steps of metastasis
• BLACK - Basement membrane invasion
• EXCLAIMED - Passage through Extra Cellular Matrix
• “I’M - Intravasation
• INSIDE - Immune interaction
• POTTER” - Platelet adhesion
• AFTER - Adhesion to endothelium
• ESCAPING - Extravasation
• AZKABAN - Angiogenesis
The Shawshank 8
(1 BM invasion) – he picks through the wall
(2 ECM passage) – the room gets filled with water
(3 intravasation) – he breaks into the sewer
(4 immune interaction) – the sewer is filled with poo
(5 platelet adhesion) – the poo is sticky
(6 adhesion to endothelium) – he adheres to the sewer using poo
(7 extravasation) – he breaks out of the sewer
(8 angiogenesis) – his new life!
Slightly more detail…• + BLACK - Basement membrane invasion - MMP (matrix
metalloproteinase) stimulation
• + Exclaimed - Passage through Extra Cellular Matrix - MMP-
• + 'im - Intravasation - MMP stimulation and altered integrins
• + Inside - Immune interaction - decreased MHC class I expression
• + Potter' - Platelet adhesion - GF release (helps it travel around)
• + AFTER - Adhesion to endothelium - CD44 expression
• + ESCAPING - Extravasation - intergin expression and MMP stimulation
• + AZKABAN - Angiogenesis - VEGF, and other angiogenic GFs
Give TWO factors which can help cells spread [2]
• Increased motility (reduced integrin expression reduces the contact between cell and stroma; reduced cadherin expression allows cells to move apart)
• Altered synthesis of enzymes that breakdown the basement membrane and stroma (matrix metalloproteinases, MMPs)
What are the THREE classes of matrix
metalloproteinases?
• Collagenases (degrade collagen I-III)
• Gelatinases (degrade collagen IV and gelatin)
• Stromelysins (degrade collagen IV and proteoglycans)
What acts to counterbalance MMPs?
• Tissue inhibitors of metalloproteinases (TIMPs)
• The balance of MMP:TIMP is important, and is a potential source of therapy
Give THREE reasons why all malignant cells don’t metastasise
[3]
• Distant site environment may be inappropriate for growth of malignant cells
• Incorrect receptors
• Metabolic factors
• Failure of angiogenesis
Give THREE mechanisms by which angiogenesis can occur
[3]• Tumour-induced stimulation of
angiogenesis (malignant cells could release angiogenic factors e.g. VEGF)
• Vasculogenic mimicry (tumour cells use their plasticity to express an endothelial phenotype to link up to the existing vascular system)
• Vessel co-option (invade into surrounding vessels, with death of lining endothelial cells leading to tumour cells lining vascular spaces)
Give an example of an anti-angiogenic factor
• Angiostatin
• Endostatin
• Vasostatin
• Thrombospondin
List FOUR factors which determine the effect a tumour
will have [4]• Site of tumour
• Extent of local spread
• Site of metastasis
• Extent of metastatic spread
• Functional effects
• Paraneoplastic effects
Give an example of a paraneoplastic effect
• Dermatomyositis (autoimmune attack of skin and muscle as a reaction to a tumour)
• Cachexia
• Anaemia
• Clubbing
You have a patient with small cell carcinoma of the lung.
What treatment option are you unlikely to carry out?
• Surgery - because by the time of diagnosis, it has almost universally metastasised
Name THREE common sites for metastatic spread in the
thorax
• Lung
• Pleura
• Mediastinal lymph nodes
What is in situ malignancy?
• An epithelial neoplasm with features of malignancy, but with no basement membrane invasion
A patient with carcinoid tumour of the jejunum with liver and bony mets
presents with flushing, diarrhoea and wheezing.
What is your diagnosis?
• Carcinoid syndrome - severe liver mets result in the failure of adequate serotonin metabolism
Give FOUR local effects of malignant neoplasias [4]
• Destruction of surrounding tissue
• Obstruction or constriction of a hollow viscus
• Ulceration
• Infiltration into NAVL
• Space-occupying lesions (eg in the brain)