Which type of tumour cells undergo invasion and metastasis?
Not all tumours undergo invasion and metastasis. Benign tumours tend to be encapsulated: they are surrounded by a capsule of connective tissue, and therefore they do not tend to invade and metastasize. Only malignant tumours tend to invade into the bloodstream and grow in another part of the body.
What is the basement membrane and what does it do?
The basement membrane is a thin sheet of fibres which are composed of collagen (the same stuff which makes your skin appear youthful). It is composed of three layers: lamina lucida, lamina densa and lamina reticularis. The function of the basement membrane is that it helps anchor down the bottom layers of epithelial tissue to the connective tissue underneath. Epithelial tissue lines organs and cavities and includes your skin.
What stages are there in the invasion/metastatic process?
In total, there are thirteen separate stages involved: some of them happen on both sides i.e. at the primary tumour site and at the metastatic site, and some of them can be attached together.
The stages include the following:
- Cells transform from normal cells into metastatic subclones:
This is done by the mutation of proto-oncogenes to oncogenes, and is discussed further in Hallmarks of Cancer.
2. Adhesion and Invasion of basement membrane
The extracellular matrix is comprised of two parts: the basement membrane and connective tissue. Cancers in early stages that invade the ECM but fail to enter the bloodstream before they are detected are known as carcinoma-in-situ. There are four steps involved in the invasion of the extracellular matrix:
- Detachment of tumour cells from one another by unzipping of the anchor protein E-cadherin.
- Degradation of the extracellular matrix by collagenase attacking the collagen fibres of the basement membrane
- Loss of adhesion of cells from integrins: this process should induce apoptosis but fails to in tumour cells.
- Migration of tumour cells through the extracellular matrix.
3. Entering of Blood Vessel, Interaction with Lymphocytes and Development of Embolus
Tumour cells are vulnerable to the effects of our immune system when they are in the circulation. The immune system constantly examines the bloodstream for foreign material, as the bloodstream is considered the biochemical highway of the human body. Most of the tumour cells float around in single formation, however they may also develop emboli as a protective mechanism. What I mean by that, is that the tumour cells aggregate (clump together), and they adhere to our white blood cells and platelets.
4. Exit blood vessel and depositing of metastatic cells
The secondary (metastatic) site at which the tumour cells decide to enter is dependent on where the primary tumour is located. The method which the cells enter the secondary site is the same as the one I discussed earlier.
Angiogenesis is defined as the production of new blood vessels, and is discussed further in Hallmarks of Cancer.
6. Growth of Metastatic Tumour
The tumour cells are dependent on receptive stroma (epithelial tissue) to grow. Therefore, not all cells that exit from the original tumour end up becoming metastatic tumours.