Characteristics of Cancer Cells

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Characteristics of Cancer Cells

• Obituary brings to light the tragedy of one local
  family (at ALE section of Website)
• Characteristics of Cancer Cells
• Have lost the genetic ability to stop dividing
• Cancer is heritableCancer cells give rise to
  cancer cells
• Immortal
• Not subject to contact inhibition
• Metastasize Spread into other tissues
• Are Dedifferentiated
• less specialized than the cell it came from)

2
The eukaryotic cell cycle is regulated by a
molecular control system

• The frequency of cell division varies with the
  type of cell
• These differences result from regulation at the
  molecular level
• Cancer cells manage to escape the usual controls
  on the cell cycle

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Figure 12.14
Evidence that Cytoplasmic Signals Control the
cell Cycle
EXPERIMENT
RESULTS
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Cytokinesis division of cytoplasm
The Cell Cycle
Mitosis division of the nucleus
Daughter cells
M-phase
G2-phase
G1-phase
Cells divide
Prep. for division organelles duplicate
Cell growth normal cell activities
Synthesis of DNA (chromosomes replicate)
Interphase G1, S, G2
S-phase
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The Cell Cycle Control System

• is like to clock
• regulated by both internal and external controls
• has specific checkpoints where the cell cycle
  stops until a go-ahead signal is received

Figure 12.15
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The Cell Cycle Control System

• For many cells, the G1 checkpoint is the most
  important
• If a cell receives a go-ahead signal at the G1
  checkpoint, it will usually complete the S, G2,
  and M phases and divide
• If the cell does not receive the go-ahead signal,
  it will exit the cycle, switching into a
  nondividing state called the G0 phase

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Regulation of Cell Division

• What evidence in your own life do you have that
  cell division is regulatedby your body?
• Left ear is about same size as right ear.
• A cut your finger heals, but the skin doesn't
  just keep growing!
• What normally controls cell division?

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Stop and Go Signs Internal and External Signals
at the Checkpoints

• Examples of internal signals
• Errors in S-phase
• molecular signal sent that prevents cell from
  leaving G2
• Kinetochore does not attach to Spindle Fiber
• molecular signal sent that delays anaphase
• An Example of an External Signal
• Growth Factors
• proteins released by certain cells that stimulate
  other cells to divide

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External Signals at the Checkpoints

• Density-dependent inhibition
• crowded cells stop dividing
• Also known as contact inhibition
• Anchorage dependence
• Most cells must be attached to a substratum in
  order to divide
• Cancer cells
• exhibit neither density-dependent inhibition nor
  anchorage dependence

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Figure 12.19
Anchorage dependence
Density-dependent inhibition (Contact Inhibition)
Density-dependent inhibition
20 ?m
20 ?m
(a) Normal mammalian cells
(b) Cancer cells
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Contact Inhibition

• Cells do not normally grow or divide when in
  contact w/ other Cells
• E.g. Cultured cells in a petri dish
• will divide until they form a layer one cell
  thick and then stop when make contact w/ other
  cells.
• Called contact inhibition of cell growth.
• Cells can migrate in culture
• Stop moving when touch other cells due to contact
  inhibition of cell movement.

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Contact inhibition does not occur in Cancerous
Cells

• Cancerous cells continue growing and moving when
  they touch other cells.
• They pile up and they migrate to other parts of
  the body -- the cancer spreads.
• Growth Factors
• made of protein
• Chemical messages that control the cell cycle
• How do we know the cell cycle is under genetic
  control?

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1. Normal cell growth
2. Basal cell carcinoma
One daughter differentiates
Both daughter cells divide
Only one daughter Cell divides
Actively dividing cells (basal cells)
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Role of Growth Factors in Normal Cells
Signaling cell
Growth factor
Growth factor binds to receptor
Receptor sets off a signal cascade to nucleus
target cell enters S-phase and divides, eventually
repairing wound
target cell
Nucleus
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Several ways to get faulty growth control in a
cancer cell
2. Mutant receptor might turn on even
without binding growth factor
1. Cell might produce its own growth factor
3. Signal cascade might occur even without
trigger from receptor
In each case, cancer cell enters S phase
and divides inappropriately, causing a tumor
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Growth Factors Stimulate Cell Division

• Diffuse through the body making contact with many
  different cells
• Bind to Membrane Receptors, like a key fitting
  into a lock.
• stimulate a pathway inside cell that leads to
  cell division.
• Each receptor binds to a different growth factor.
• Different cell types are stimulated by different
  growth factors.

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Cancer Its all in the Genes

• Proto-oncogenes
• Genes that code for growth factors
• Active in actively dividing tissues (e.g. skin)
• Sometimes mutate into......
• Oncogenes
• genes that cause cancer
• produce too much growth factor
• Over stimulate mitosis
• Oncogenes are rarely inherited.....Why?

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Tumor Suppressor Genes

• Tumor Suppressor Genes
• Code for Proteins that turn off cell division
• e.g. p53 gene
• p53 Gene
• Codes for a protein that stops the cell cycle
  after G1
• Half of all cancers involve p53
• One mutant Tumor Suppressor Gene does not cause
  cancer....Why?

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p53 A Tumor Suppresser Gene

• How many p53 genes did you inherit? Why?
• How many p53 genes need to mutate before a cell
  becomes cancerous? Why?

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BRCA 1 Breast Cancer Susceptibility Gene

• BRCA 1 is a Tumor Suppresser gene
• If a women inherits BRCA 1 she has a
• 80 to 90 chance of developing breast cancer
• 40 to 50 chance of ovarian cancer.
• Why arent the percentages 100?
• Why are the percentages much lower for the
  average woman?

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Figure 12.20
The growth and metastasis of a malignant breast
tumor
Lymph vessel
Tumor
Bloodvessel
Cancercell
Glandulartissue
Metastatictumor
A tumor growsfrom a singlecancer cell.
Cancer cells invade neighboringtissue.
Cancer cells spreadthrough lymph andblood
vessels to other parts of the body.
Cancer cells may survive and establisha new
tumor in another part of the body.
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3
2
1
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The Role of the Environment in Causing Cancer

• Certain Viruses, toxins, or Radiation may lead to
  a p53 mutation
• A 2nd p53 mutation may lead to one of the
  following cancers
• Cancer of the....
• Bladder, blood, brain, breast, colon,
  esophagus, liver, lung, spleen, thyroid, etc.

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Therapeutic Strategies for Treating Cancer

• Slash Burn Poison!!
• Since cancer is uncontrolled cell division, all
  chemotherapeutic treatments involve the cell
  cycle.
• Phase-specific chemotherapies
• Prevent cells from entering S-phase
• Block the S-phase
• Block the M-phase (mitosis)

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Phase-specific Chemotherapies

• Prevent cells from entering the S-phase
• Block Growth factor receptors on cell membrane
  with antibody (e.g. Herceptin)
• Block the S phase
• Thioguanine and Methotrexate and other
  chemotherapeutic drugs block DNA synthesis
• Block or stop mitosis
• Taxol interferes with the movement of the
  chromosomes along spindle fibers

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Cells Affected by Chemotherapy

• Chemo may affect all dividing cells
• Which cells divide rapidly?
• Hair follicle cells
• Skin cells
• Cells lining digestive tract
• Blood stem cells
• Divide to produce???
• So.... what would be the side effects?

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Side Effects of Chemotherapy

• Baldness
• Cuts and wounds heal slowly
• Destroy lining of digestive tract
• nausea and severe bacterial infection
• Decrease Blood cell Production
• RBCs ? Anemia
• WBCs ? decreased ability to fight infections and
  kill cancer cells

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How to Lower your Cancer Risks

• Eat plenty of fiber
• Fiber speeds passage through digestive tract
• Do not smoke
• Drink alcohol in moderation or not at all
• Exercise regularly
• Do not become overweight
• Limit dietary fat
• Limit sun exposure or use sunscreen (SPF 30)
• Learn to recognize the warning signs of cancer

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Common Warning Signs of Cancer C.A.U.T.I.O.N.

• C - change in bowel or bladder habits
• A - a sore that does not heal
• U - unusual bleeding or discharge
• T - thickening or lump in the breast or any
  part of the body
• I - indigestion or difficulty swallowing
• O - obvious change in a wart or mole
• N - nagging cough or hoarseness