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)