Haematological malignancies occur in cells which are already anchorage-independent and circulating. However, additional features are required for a solid tumor to grow and metastasise. The acquisition of additional mutations means that the secondary tumor cells may replicate faster than the primary, or be unable to differentiate as fully.
The blood supply to the enlarging mass of cells is initially rate-limiting, as evidenced by the ischaemic centers to solid Tumours. Some Tumours may acquire mutations to enhance the secretion of factors to stimulate neovascularisation (angiogenesis), but in many instances physiology suffices since hypoxia is a potent stimulus of the angiogenic factor VEGEF (vascular endothelial cell growth factor).
Metastasis, the cardinal feature of most malignant Tumours, requires a cancer cell to have the ability to detach from its surroundings without undergoing apoptosis. Certain mutations result in nuclei receiving signals as if they were anchored to local structures – for example, mutations in APC (See Fig: 1.18). In addition, metastasising cells must acquire the novel abilities to invade through local tissues to reach blood vessels, survive in the circulation, adhere to a blood vessel wall and migrate into the new tissue. Many of these features are facilitated by the synthesis of novel cellular adhesion molecules or tissue-degradative enzymes such as metalloproteinases. The adherence to the endothelium in the new site can not simply reflect the fact that the cells adhere to the nearest capillary bed, since metastases display tissue specificity – for example, thyroid cancer to bone. Specific cellular adhesion mechanisms analogous to those used by inflammatory cells are thought to operate. In addition, to escape destruction by cells of the immune system, tumour cells may down-regulate cell-surface expression of recognition molecules or induce a general depression of immune responses. From the book of:
DAVIDSON’S
Principles and Practice of Medicine
Eighteenth Edition
No comments:
Post a Comment