Altered Cellular Proliferation and Differentiation
In terms of cancer, if we look at the areas that continually proliferate, they are more apt to
develop cancer. i.e skin and respiratory continually regenerate itself. However cardiac and nerve
muscles do not. Thus, are more unlikely to develop it.
*** Poorly undifferentiated cancer is harder to treat.
Cellular Proliferation: the generation of new, daughter cells which divide from parent cells.
Meiosis- is a process of dividing germ cells resulting in sperm and ovum. Would result in
inherited cancers, which are only around 1%
Mitosis- is division and proliferation of all nongerm cells. Occurs continuously.
Cellular Differentiation: The orderly process of cellular maturation to achieve a specific
Stem Cells: ** Undifferentiated are valued for flexibility/adaptability
Highly undifferentiated units (they are flexible and able to adapt to be specialized for
different parts of the body)
Have the potential to divide into progenitor cells (parent cells), maturing into
differentiated units with special function
With differentiation, cells lose their ability to flexibly respond and adapt
Differentiated cells carry out important physiological functions (RBCs with blood loss) Altered cellular proliferation and differentiation
Cellular proliferation and differentiation is under the control of genes
Neoplastic cells ignore genetic controls resulting in:
1. Autonomy: Excessive cellular proliferation
2. Anaplasia: Loss of cellular differentiation
Altered genes leading to cancer
1. Mutator genes- control repair of DNA and self destruct abnormal cells.
2. Oncogenes- promote unregulated cell growth and development
- Conversion of a normal protooncogene, which regulate cell function. When activated
can become oncogenes thorugh: point mutation, translocation (chromosome breaks,
relocated or unites), or gene amplification (altering chromosomes by accelerating the
replication of genes. ** over producing gene products.
3. Tumor suppressor genes- regulate cell proliferation and regulate apoptosis (P53,
responsible for opposing cell division in response to cell DNA damage, by delaying cell
development, so that there is time for DNA repair).
- Rb gene, rare childhood cancers, germ line mutations
Carcinogenesis (development of cancer)
1. Initiation event- causes the mutation in a cell.
2. Promoting event- expansion of the mutated cell growth and reproduction. Growth of the
cell depends on continued exposure to the promoter (ie. Chronic inflammation,
3. Progression event- cancer growth no longer depends on the promoter.
Carcinogens- known cancer causing agents
1. Radiation- releases O2 radicals, which cause damage to other cells which cause an
inflammatory response and an over aggressive immune system. Sometimes only used to
prolong life, as certain body parts can only be radiated once. Can cause severe burns (just
like the sun light)
2. Reactive oxygen species- like food additives/ need neutralizing enzymes to deal with it.
3. Hormones- can cause growth/ Tomoxifican is a drug used to block estrogen which feeds
4. Tobacco- causes DNA mutations
5. Infectious microorganisms- H pylori- creates ongoing inflammation which causes
dysplasic changes and increases risk of cancer. Don’t ignore heart burn!
6. Certain chemicals Impact of Cancer on Tissues, organs and organ systems
1. Autonomy: Unregulated proliferation
2. Anaplasia- Loss of cell differentiation (poorly differentiated)—on exam!!!
3. Loss of cell to cell communication
4. Increased energy expenditure- because it takes nutrients and blood supply
5. Increased motility and loss of cohesion
6. Rapid angiogenesis (extensive blood flow)
7. Substance secretion- some tumors stimulate release of more estrogen
8. Present foreign antigens on the cancer cell surface; stimulating the immune response
Local spread- stays within the tissue of origin
Direct extension- process of tumor cells moving into adjacent tissues and organs.
- penetration of the basement membrane.
- Neoplastic cells adhere to the ECM by expressing adhesion molecules.
- Tumor then releases enzymes to dissolve ECM
Seeding- breaking into neighborhood tissue (usually in peritoneal/ ple