Carcinomas (most prominent @90%) arise from epithelial cells (from external
and internal body surfaces).
Sarcomas arise from supporting tissues (bone, cartilage, fat, muscle
etc.)
Lymphomas (lymphatic) and leukemia (blood) are proliferating cell free
in the fluid systems not as solid masses
Tumours arise from uncontrolled cell division from a
loss of balance between cell division and cell differentiation.
The basal layer of epithelial cells
can begin to grow more than the surrounding cells to form a tumour.
Defective cell cycle control mechanisms can lead to uncontrolled cell
proliferation to form a tumour.
Benign tumours do not spread but malignant tumours invade neighbouring
tissues and may undergo metastasis.
Special Characteristics of Cancer Cell Growth
1) Anchorage-independent growth
Most cell require a supporting surface and will grow in a monola.yer
in culture.
Cancer cells can grow suspended in liquid or semi-solid media
2) Reduced sensitivity to density dependent inhibition of growth
In culture, most normal cells divide until a monolayer is formed
Cancer cells "pile up".
Angiogenesis, the growth of supporting blood vessels, is required
for tumours to grow to more that a few millimetres in diameter.
Controlled by a balance of activators and inhibitors of angiogenesis
including VEGF and FGF.
Metastasis and Invasion
Primary cancers are often cured by surgical removal of the tumour.
However, if the cancerous cells have started to spread through the
body more treatment is needed.
Invasion is the direct migration and penetration of cancer cells into
adjacent tissues.
Metastasis is the movement of cancer cells
into the blood stream (or other fluid systems) to travel to distant sites
to establish and form a tumour.
These processes require changes in cell adhesion, motility and the production
of proteases that degrade protein-based physical barriers to cell movement.
Cancer cells can be selected for the ability
to metastasize (as can be demonstrated in mice).
Metastasis can be blocked by the immune system.
Causes of Cancer include Cigarette Smoking and other carcinogens.
The development of cancer
The main stages of cancer development are 1)
initiation, 2) promotion and 3) progression.
Oncogenes, which can induce cancer, arise from as mutant forms of proto
oncogenes which are really normally and usually essential cellular genes.
In fact, most are members of growth factor signaling pathways.
Cancer can arise from the loss of tumour suppressor genes that normally
function to restrain cell proliferation
Defective DNA Repair can contribute to cancer by allowing multiple
mutations to accumulate to cause the disease state.
Proto-oncogenes are normal cellular genes
These are usually involved in growth or the control of growth.
Can become an oncogene by 1) point mutation,
2) Gene amplification, 3) Chromosomal translocation, 4) local DNA rearrangements
or 5) Insertion mutagenesis.
Tumour suppressor genes
Hereditary cancers often arise from a germ-line
mutation in a tumour suppressor gene followed by a somatic mutation.
The human papillomavirus (cervical cancers)
produce protein E6 & E7 that bind to Rb protein
and disrupt the ability to halts cells at check point to lead to uncontrolled
proliferation.
Although current treatments mostly involve radiation and chemotherapy to kill rapidly dividing cancerous cells, less damaging treatments are under development including immunotherapy and gene therapy.
Notes prepared from Becker's World of the Cell, 8th edition
Hardin, Bertoni & Kleinsmith, 2012
Figures copyright of Pearson Education Inc.
email me at bestave@mun.ca