Neoplastic growth, histogenesis and structure characteristics. Precancer. General histological features of benign, malignant; epithelial and mesenchymal tumours.
There are a number of characteristic features of neoplastic growth that we shall consider here:
- Failure of contact inhibition
- Normal cells will stop cellular proliferation when they bump against other cells, this is not the case in cancer cells. The failure of this is thought to relate to the tumor suppressor gene NF2 which codes for merlin, a protein that supports cadherin-mediated contact inhibition.
- Evasion of cell death
- There are two apoptotic pathways, extrinsic (where the TNF receptor is externally activated) and the intrinsic mitochondrial pathway.
- Within these pathways, cancer cells have the opportunity to disrupt in a number of ways, the most commonly cited is the mutation of BCL2 gene, causing overexpression of BCL2 protein, protecting a cell from apoptosis.
- Limitless replicative potential
- Most cells have cellular senescence, a replication limit due to the progressive shortening of telomeres.
- The short telomeres are generally picked up by cellular checkpoints, in a cancer cell, where the checkpoints are non-functioning and telomerase is reactivated, we see a limitless level of cellular reproduction.
- Sustained Angiogenesis
- Cancer cells have increased metabolic needs, as such, they need a strong blood supply. They get this by triggering angiogenesis through the actions of HIF-1 alpha (hypoxia-inducible factor 1 alpha), an oxygen sensitive transcription factor. This triggers transcription of the proangiogenic factor VEGF.
- Ability to Metastasize
- Malignant neoplasms are able to metastasize, that is to say, the spread through the bodies blood or lymphatic system to form secondary metastatic tumours. The process for doing so is as follows:
- Cancer cells begin by loosening intercellular junctions between them
- Then they trigger degradation of the type IV collagen in the ECM
- They then attach to the basal membrane
- Finally they migrate through the basal membrane and into the bloodstream.
- From here they are able to form a tumor cell embolus, and go on to adhere to the basement membrane elsewhere.
- They then undergo extravasation and the metastatic tumour begins to take root.
- Evasion of the immune system
- Cancerous cells are able to avoid the immune system by a number of different features, not only does their DNA alter, creating a genetically heterogeneous structure but they are also able to directly deactivate T-cells. For instance PDL1 probe on the cancer cell binds to a PD1 receptor on the T-cell making it inactive