Session 9 Flashcards
What must malignant cells do to get from a primary site to a secondary site?
Grow and invade at the primary site
Enter a transport system and lodge at a secondary site and exit the vessel (extravasation).
Grow at the secondary site to form a new tumour (colonisation)
Evade destruction from immune cells at all points
What does invasion into surrounding tissue by carcinoma cells require and what is the name of this process?
Altered adhesion, stromal proteolysis and altered motility.
This results in a carcinoma cell phenotype that appears more like a mesenchymal cell than a epithelial cell, hence this is called epithelial to mesenchymal transition (EMT).
What does altered adhesion of malignant cells involve?
Altered adhesion between malignant cells involves a reduction is E-cadherin expression. Altered adhesion between malignant and stromal proteins involves changes in integrin expression.
What does stromal proteolysis of malignant cells involve?
The cells degrade the basement membrane and stroma to invade through changes in expression of proteases, notably matrix metalloproteinases (MMPs).
What does altered motility of malignant cells involve?
Changes in the actin cytoskeleton.
How does a cancer niche form and what does it do?
Forms when malignant cells take advantage of nearby non-neoplastic cells (e.g. Fibroblasts, inflammatory cells, endothelial cells). They provide some growth factors and proteases.
Where can malignant cells enter?
Blood vessels via capillaries and venules.
Lymphatic vessels.
Fluid in body cavities (pleura, peritoneal, pericardial, brain ventricles), which is known as transcoelomic spread.
What is tumour dormancy, what causes it and what can it result in?
An apparent disease free individual can harbour many micrometastases. If these start to grow a malignant neoplasm can relapse years after an apparent cure.
Micrometastases form when malignant cells lodge at a secondary site and fail to grow (can be due to an immune attack, no angiogenesis or a hostile secondary site).
What does the site of a secondary neoplasm depend on?
- Regional drainage of blood, lymph or coelomic fluid. Blood borne metastases is often to the next capillary bed. Lymphatic metastases predictably drain to the regional lymph node. Transcoelomic spread is predictably to other areas in the coelomic space of per adjacent organs.
- The seed and soil effect phenomenon, which explains the seemingly unpredictable distribution of blood borne metastases. It is due to interactions between malignant cells and the local tumour environment (niche) at the secondary site.
How do carcinomas and sarcomas typically spread?
Carcinomas typically spread via lymphatics first. Sarcomas typically spread via the blood stream.
Where are common sites for blood borne metastases and from what neoplasms are they commonly from?
Lung - breast, stomach, large intestine carcinomas
Bone - bronchial, breast, thyroid, renal and prostate carcinomas
Liver - from carcinomas of large intestine
Brain - bronchial, breast, testicular carcinomas and malignant melanoma
Give an example of a malignant neoplasm that metastasises very early and one that never metastasises
Early - bronchial small cell carcinoma
Never - basal cell carcinoma of the skin
What are direct local effects of primary/secondary neoplasms?
Direct invasion and destruction of normal tissue
Ulceration of a surface leading to bleeding
Compression of adjacent structures
Blocking of tubes or orifices
What are indirect systemic effects of primary/secondary neoplasms?
Increasing tumour burden - parasitic effect on the host. Along with secreted factors (e.g.cytokines) this leads to decreased appetite, cachexia, malaise, immunosuppression and thrombosis.
Hormones - can be secreted from well differentiated benign tumours of endocrine glands (e.g. Thyroid adenoma produces thyroxine) or malignant tumours (e.g. Bronchial small cell carcinoma can produce ACTH and bronchial squamous cell carcinoma can produce PTH like hormone).
Miscellaneous - itchy skin, abnormal pigmentation, fever and myositis.
