Principles of Cell Biology (BIOL2060)

Department of Biology
Memorial University of Newfoundland

Cancer

Complex disease arising from abnormalities in cell division.
Predictions are that ~ one half of North Americans will eventually develop cancer .
Second leading cause of death (cardiovascular disease is number 1).

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, 9th edition
Hardin & Bertoni, 2015
Figures copyright of Pearson Education Inc.
email me at bestave@mun.ca