Cancer cell characteristics and attributes:
- Altered cell morphology: cancer cells usually have a much more rounded shape, reflecting a much less organised arrangement of the cytoskeletal elements.
- Different cell surface: although the relative amounts of the 4 main phospholipids of the bilayer are unaltered, there are significant alterations to the glycolipid and glycoprotein content of the cell membrane. In particular there is a reduction in the amount of the extracellular glycoprotein fibronectin. This glycoprotein plays a role in the anchorage of cells.
- Increased rate of glycolysis: those cancer c3lls which form solid tumours have been shown to have higher glycolytic activity . This cannot be accounted for by the faster rate of proliferation, but appears to be the result of an uncontrolled elevation in the rate of glucose uptake into the cell.
- Lack of contact inhibition: Whereas normal cells wgrowing in culture will cease to grow when they make physical contact with neighboring cells, this does not occur with transformed cells. Thus the latter continue to grow and reach higher densities than their normal counterparts.
- Anchorage-independent growth: Most normal cells will only grow in culture if attached to a solid surface forming a thin carpet of cells. In contrast cancer cells re anchorage independent, and can grow in suspension culture as unattached cells. For some transformed cells, this is the result of them producing one of the TGF’s.
- Diminished requirement for growth factors: Many cancer cells can grow in culture medium supplemented with much less serum than required by their normal counterparts. This different reflects a reduced dependence on the growth factors supplied by the serum. For some cancer cells this arises when the transformed cells begin to uncontrollably produce GF’s for which they already produce the corresponding receptor. This is referred to as Autocrine stimulation.
- Susceptibility to anti-metabolites: Many cancer cells have lost the control mechanism that sends nutritionally limited normal cells into G1 quiscence. Thus if these cells are prevented from dividing, a spectrum of cells are produced which are blocked at different stages of the cycle. Thus they are less viable and die off more rapidly. This is the basis for antimetabolites.
Mechanism for cellular transformation:
- Chromosomal abnormalities: alterations to chromosomes such as deletions, translocation of segments and inversions of chromosomal components are often involved in the initiation and progression of certain human cancer. For example retinoblastoma and Burkitts lymphoma.
- Environmental and chemical carcinogens: things such as UV, ionizing radiation and chemicals such as formaldehyde and others have been implicated in the development of cancer. Although known carcinogens are diverse, they all have one common property- they mutate DNA of the target cells.
- Oncogenic viruses: To date, viruses that induce cancer include a small number of DNA tumor viruses and well as the RNA-containing retroviruses. In general the oncogenes of DNA viruses encode for viral products that are required for normal replication of the virus. In contrast most of the oncogenes associated with retroviruses are genes accidentally acquired from a host cells DNA, which have been incorporated into the viral genome.
- Normal genes with the potential to become oncogenes are called proto-oncogenes.
Mechanism by which cancer drugs select for cancer cells:
- Based on cancer cells dividing uncontrollably and being accumulated more readily into rapidly-dividing cells.
- Genotoxic agents affect the integrity of DNA-
- Anti-metabolites affect enzymes involved in DNA synthesis
- Spindle inhibitors affect cell division
- Endocrine interfering drugs affect transcription in hormones sensitive tumor cells.
- Plus some more, all which target cells that are undergoing rapid DNA rep and cell division.