Lecture 11.

• Basal Lamina.

  - Layer supporting stem cells, maintains non-differentiation.
• Stem Cells.

  - Cells with high potential to become cancerous.
• Differentiation.

  - Process ensuring cells become specialised, preventing cancer.
• Proliferation Signals.

  - Signals regulating cell growth and division

  - Signals from neighbouring cells.
• Endogenous Signals.

  - Internal signals affecting cell behaviour, like insulin

  - Cellular = pH, O2 levels (hypoxic).
• Exogenous Signals.

  - External factors influencing cell proliferation.

  
• Why would the cells on the left proliferate, compared to the cells on the right?

  - More space to grow and divide

  - Right cells have "signals" to detect that the petri dish is full

  - Signals from neighbouring cells also indicate this

  - Endogenous signals from neighbours, and nutrients

  - Anchorage dependence (i.e. a floor)

  - Density dependent inhibition

  - Age.
• Anchorage Dependence.

  - Requirement for cells to attach to grow.
• Density Dependent Inhibition.

  - Growth regulation based on cell population density.
• What could we do to encourage the cells to proliferate even faster?

  - Growth factors (e.g. PDGF = Platelet-derived growth factor)

  - Changing temperature
• Hayflick Limit.

  - Maximum number of cell divisions, 40-50 times.
• Telomeres.

  - Protective caps on chromosomes that shorten with division

  - Too short = cell cannot proliferate, enters a state of senescence or apoptosis.

  
• Telomerase.

  - Enzyme extending telomeres, allowing continued cell division

  - E.g. cancer and stem cells, bypass Hayflick limit

  - Activate telomerase.
• Hyperplasia.

  - Increased cell production, can be healthy or pathological

  - E.g. uncontrolled production of thyroid cells.

  
• Hypertrophy.

  - Increase in tissue size without increased cell number

  - Common in muscles (mature muscles fibres don't proliferate)

  - E.g. swelling

  - Can be healthy or pathological e.g. inflammatory.

  
• Atrophy.

  - Reduction in cell size and/or number

  - Can be healthy or pathological.
• Metaplasia.

  - Change of one cell type to another

  - E.g. one mature tissue types replaces another mature tissue type

  - Can be healthy (scar tissue) or pathological.
• Anaplasia.

  - Loss of differentiation in cells, often cancerous

  - Revert to potent state

  - Display pleomorphism = indicator of malignancy.

  
• Pleomorphism.

  - Variation in cell size and shape.
• What is cancer?

  - Uncontrolled tissue proliferation threatening health

  - Harmful cancers = beyond proliferation, cause harm

  - Variable in morphology, severity & prognosis.
• Leukemia.

  - Cancer of white blood cells with poor prognosis.
• Pancreatic Cancer.

  - Late detection, poor prognosis, invasive.
• Tumour.

  - Abnormal growth of tissue

  - Not all tumours are cancers, and not all cancers are tumours.
• Neoplasia.

  - Abnormal proliferation of cells.
• Malignant Cancer.

  - Cancer that invades surrounding tissues

  - Some cancers can have abnormal growth, but is not malignant.
• Benign Tumour.

  - Non-invasive abnormal tissue growth.
• Self-Sufficiency.

  - Normal cells proliferate after receiving mitogenic growth signals

  - Cancer cells bypass growth signals.
• KRAS, RAS and HER2 receptor.

  -KRAS = mutations in this proto-oncogene leads to uncontrolled cell growth and cancer

  -RAS (family of proteins, including KRAS) = mutations lead to cancers

  -HER2receptor = protein that promotes growth of cancer cells.

  
• Oncogenes.

  - Mutations promoting cancer cell proliferation.
• Tumour Suppressor Genes.

  - Regulate and inhibit cell division.
• What are the two pathways towards uncontrolled cell prolfieration?

  - Tumour suppressor gene is mutated = inactivated, cannot code for protein or dysfunctional

  - > uncontrolled proliferation

  - Normal regulatory genes = stimulate or inhibit proliferation.
• p53 Gene.

  - Tumour suppressor, regulates cell cycle

  - Triggers cell to undergo DNA repair.

  
• Telomere shortening.

  - Telomere maintenance = replicative potential

  - Many malignant cells have upregulated expression of telomerase

  - Telomeric sequences lost from tips of chromosomes with every DNA replication

  - If normal cell divides too many times = telomeres become too short to protect ends of chromosomes

  - Pathway to halt cell division initiated

  - Cancer cells express telomerase = maintains telomere length.
• Angiogenesis.

  - Formation of new blood vessels.
• Vascularisation.

  - The process of growing blood vessels into a tissue to improve oxygen and nutrient supply.
• VEGF (vascular endothelial growth factor).

  - Protein stimulating blood vessel formation.
• Inducing angiogenesis.

  - All cells in a tissue must be close to a capillary blood vessel

  - After development = process of angiogenesis carefully regulated

  - Cells within abnormalative lesions must be angiogenic to expand.

  
• Endothelial Cells.

  - Cells lining blood vessels, crucial for angiogenesis.
• Angiogenesis - endothelial cells.

  - Blood supply required for embryogenesis = tissue remodelling & repair

  - Endothelial cells make new vessels = duplication of existing endothelial cells

  - All new vessels begin as capillaries = branch from existing capillaries

  - VEGF = endothelial cells receive signal > begin to proliferate > form new vascular tube.

  
• Capillary Formation In Vitro.

  - Oxygen-deprived cells release angiogenic factors

  - Induce capillary growth in their direction.