Altered Cell Growth and Altered Cell Growth and Cancer DevelopmentCancer Development

CancerCancer The division of normal cells is precisely The division of normal cells is precisely

controlled. New cells are only formed for controlled. New cells are only formed for growth or to replace dead ones.growth or to replace dead ones.

Cancerous cells divide repeatedly out of Cancerous cells divide repeatedly out of control even though they are not needed, they control even though they are not needed, they crowd out other normal cells and function crowd out other normal cells and function abnormally. They can also destroy the correct abnormally. They can also destroy the correct functioning of major organs.functioning of major organs.

What causes cancerWhat causes cancer ? ? Cancer arises from the Cancer arises from the mutationmutation of a normal gene. of a normal gene. Mutated genes that cause cancer are called Mutated genes that cause cancer are called

oncogenesoncogenes.. It is thought that several mutations need to occur to It is thought that several mutations need to occur to

give rise to cancergive rise to cancer Cells that are old or not functioning properly normally Cells that are old or not functioning properly normally

self destruct and are replaced by new cells.self destruct and are replaced by new cells. However, cancerous cells do not self destruct and However, cancerous cells do not self destruct and

continue to divide rapidly producing millions of new continue to divide rapidly producing millions of new cancerous cells.cancerous cells.

A factor which brings about a mutation is called A factor which brings about a mutation is called a a mutagen.mutagen.

A mutagen is A mutagen is mutagenic.mutagenic.

Any agent that causes cancer is called a Any agent that causes cancer is called a carcinogencarcinogen and is described as and is described as carcinogeniccarcinogenic..

So some mutagens are carcinogenic.So some mutagens are carcinogenic.

CarcinogensCarcinogens Ionising radiationIonising radiation – X Rays, UV light – X Rays, UV light

ChemicalsChemicals – tar from cigarettes – tar from cigarettes

Virus infectionVirus infection – papilloma virus can be responsible for – papilloma virus can be responsible for cervical cancer.cervical cancer.

Hereditary predispositionHereditary predisposition – Some families are – Some families are more more susceptiblesusceptible to getting certain cancers. Remember to getting certain cancers. Remember you you can’t inherit cancercan’t inherit cancer its just that you maybe more its just that you maybe more susceptible to getting it.susceptible to getting it.

The Development of The Development of CancerCancer

Within every nucleus of every one of the Within every nucleus of every one of the human body's 30 trillion cells exists DNA, the human body's 30 trillion cells exists DNA, the substance that contains the information substance that contains the information needed to make and control every cell within needed to make and control every cell within the body. Here is a close-up view of a tiny the body. Here is a close-up view of a tiny fragment of DNA.fragment of DNA.

1. DNA of a normal cell1. DNA of a normal cell

This piece of DNA is an exact copy of the DNA from which it came. This piece of DNA is an exact copy of the DNA from which it came.

When the parent cell divided to create two cells, the cell's DNA also When the parent cell divided to create two cells, the cell's DNA also

divided, creating two identical copies of the original DNA. divided, creating two identical copies of the original DNA.

2. Mutation of DNA2. Mutation of DNA

Here is the same section of Here is the same section of DNA but from another cell. If DNA but from another cell. If you can imagine that DNA is a you can imagine that DNA is a twisted ladder, then each rung twisted ladder, then each rung of the ladder is a pair of joined of the ladder is a pair of joined molecules, or a base pair. With molecules, or a base pair. With this section of DNA, one of the this section of DNA, one of the base pairs is different from the base pairs is different from the original. original.

This DNA has suffered a This DNA has suffered a mutationmutation, either through mis-, either through mis-copying (when its parent cell copying (when its parent cell divided), or through the divided), or through the damaging effects of exposure to damaging effects of exposure to radiation or a chemical radiation or a chemical carcinogen.carcinogen.

3. Genetically altered cell3. Genetically altered cell

Body cells replicate through mitosis, they respond to their surrounding cells Body cells replicate through mitosis, they respond to their surrounding cells

and replicate only to replace other cells. Sometimes a and replicate only to replace other cells. Sometimes a genetic mutationgenetic mutation will will

cause a cell and its descendants to reproduce even though replacement cause a cell and its descendants to reproduce even though replacement

cells are not needed.cells are not needed.

The DNA of the cell highlighted above has a The DNA of the cell highlighted above has a mutationmutation that causes the cell to that causes the cell to

replicate even though this tissue doesn't need replacement cells at this time replicate even though this tissue doesn't need replacement cells at this time

or at this place.or at this place.

4. Spread and second 4. Spread and second mutationmutation

The genetically altered cells have, over time, The genetically altered cells have, over time, reproduced reproduced uncheckedunchecked, crowding out the surrounding normal cells. The , crowding out the surrounding normal cells. The growth may contain one million cells and be the size of a growth may contain one million cells and be the size of a pinhead. At this point the cells continue to look the same as the pinhead. At this point the cells continue to look the same as the surrounding healthy cells. surrounding healthy cells.

After about a million divisions, there's a good chance that one After about a million divisions, there's a good chance that one of the new cells will have of the new cells will have mutated furthermutated further. This cell, now . This cell, now carrying two carrying two mutant genesmutant genes, could have an , could have an altered appearancealtered appearance and be even more prone to reproduce unchecked.and be even more prone to reproduce unchecked.

5. Third mutation5. Third mutation

Not all mutations that lead to cancerous cells result in the cells Not all mutations that lead to cancerous cells result in the cells reproducing at a faster, more uncontrolled rate. For example, a reproducing at a faster, more uncontrolled rate. For example, a mutation may simply cause a cell to keep from self-destructing. mutation may simply cause a cell to keep from self-destructing. All normal cells have surveillance mechanisms that look for All normal cells have surveillance mechanisms that look for damage or for problems with their own control systems. If such damage or for problems with their own control systems. If such problems are found, the cell destroys itself.problems are found, the cell destroys itself.

Over time and after many cell divisions, a Over time and after many cell divisions, a third mutationthird mutation may may arise. If the mutation gives the cell some further advantage, that arise. If the mutation gives the cell some further advantage, that cell will grow more vigorously than its predecessors and thus cell will grow more vigorously than its predecessors and thus speed up the speed up the growth of the tumourgrowth of the tumour..

6. Fourth mutation6. Fourth mutation

The new type of cells grow rapidly, allowing for more The new type of cells grow rapidly, allowing for more opportunities for mutations. The next mutation paves the opportunities for mutations. The next mutation paves the way for the development of an even more way for the development of an even more aggressive aggressive cancercancer. .

At this point the tumour is still containedAt this point the tumour is still contained..

7. Breaking through the 7. Breaking through the membranemembrane

The newer, wilder cells created by another mutation The newer, wilder cells created by another mutation are able to are able to push their way through the epithelial push their way through the epithelial tissue's basement membranetissue's basement membrane, which is a meshwork of , which is a meshwork of protein that normally creates a barrier. The invasive protein that normally creates a barrier. The invasive cells in this tumour are cells in this tumour are no longer containedno longer contained. .

At this point the cancer is still At this point the cancer is still too small to be detectedtoo small to be detected..

8. Angiogenesis8. Angiogenesis

Often during the development of earlier stages of the tumour, or Often during the development of earlier stages of the tumour, or perhaps by the time the tumour has broken through the perhaps by the time the tumour has broken through the basement membrane (as pictured above), basement membrane (as pictured above), angiogenesis angiogenesis takes takes place. place. Angiogenesis is the recruitment of blood vessels from Angiogenesis is the recruitment of blood vessels from the network of neighbouring vessels. the network of neighbouring vessels.

Without blood and the nutrients it carries, a tumour would be Without blood and the nutrients it carries, a tumour would be unable to continue growing. With the new blood supply, unable to continue growing. With the new blood supply, however, the however, the growth of the tumour acceleratesgrowth of the tumour accelerates; it soon contains ; it soon contains thousand million cellsthousand million cells and, now the size of a small grape, is and, now the size of a small grape, is large enough to be detected as a lump large enough to be detected as a lump

9.Invasion and dispersal9.Invasion and dispersal

The tumour has now The tumour has now invaded the tissueinvaded the tissue beyond the beyond the basement membrane.basement membrane.

Individual cells from the tumour enter into the network Individual cells from the tumour enter into the network of newly formed blood vesselsof newly formed blood vessels, using these vessels as , using these vessels as highways by which they can move to other parts of the highways by which they can move to other parts of the body. A tumour as small as a gram can send out a body. A tumour as small as a gram can send out a million tumour cells into blood vessels a day.million tumour cells into blood vessels a day.

10. Tumour cells travel - 10. Tumour cells travel - metastasismetastasis

What makes most tumours What makes most tumours so lethal is their ability to so lethal is their ability to metastasize metastasize -- that is, -- that is, establish new tumour sites establish new tumour sites at other locations throughout at other locations throughout the body.the body.Secondary tumoursSecondary tumours..

Metastasis is now underway, Metastasis is now underway, as tumour cells from the as tumour cells from the original cancer growth travel original cancer growth travel throughout the body. Most of throughout the body. Most of these cells will die soon after these cells will die soon after entering the blood or lymph entering the blood or lymph circulation.circulation.

11. Metastasis11. Metastasis

To form a To form a secondary tumoursecondary tumour, a tumour cell needs to leave the , a tumour cell needs to leave the vessel system and invade tissue. The cell must vessel system and invade tissue. The cell must attach itselfattach itself to a to a vessel's wall. Once this is done, it can work its way through the vessel's wall. Once this is done, it can work its way through the vessel and enter the tissue. vessel and enter the tissue.

Although perhaps less than one in 10,000 tumour cells will Although perhaps less than one in 10,000 tumour cells will survive long enough to establish a new tumour site, a few survive long enough to establish a new tumour site, a few survivors can escape and initiate survivors can escape and initiate new coloniesnew colonies of the cancer. of the cancer.

PathophysiologyPathophysiology HypertrophyHypertrophy is cell growth that causes is cell growth that causes

tissue to increase in size by enlarging tissue to increase in size by enlarging each cell.each cell.

Hyperplasia Hyperplasia is growth that causes tissue is growth that causes tissue to increase in size by increasing the to increase in size by increasing the number of cells.number of cells.

Neoplasia Neoplasia is any new or continued cell is any new or continued cell growth not needed for normal growth not needed for normal development or replacement of dead and development or replacement of dead and damaged tissues.damaged tissues.

Characteristics of Normal Characteristics of Normal CellsCells Have limited cell divisionHave limited cell division Undergo apoptosisUndergo apoptosis Show specific morphologyShow specific morphology Have a small nuclear-cytoplasmic ratioHave a small nuclear-cytoplasmic ratio Perform specific differentiated Perform specific differentiated

functionsfunctions Adhere tightly togetherAdhere tightly together

(Continued)(Continued)

Characteristics of Normal Characteristics of Normal CellsCells (Continued)(Continued)

NonmigratoryNonmigratory Grow in an orderly and well-regulated Grow in an orderly and well-regulated

mannermanner Contact inhibited Contact inhibited EuploidEuploid

Characteristics of Cancer Characteristics of Cancer CellsCells

Have rapid or continuous cell divisionHave rapid or continuous cell division Do not respond to signals for apoptosisDo not respond to signals for apoptosis Show anaplastic morphologyShow anaplastic morphology Have a large nuclear-cytoplasmic ratioHave a large nuclear-cytoplasmic ratio Lose some or all differentiated functionsLose some or all differentiated functions Adhere loosely togetherAdhere loosely together

(Continued)(Continued)

Characteristics of Cancer Characteristics of Cancer CellsCells (Continued)(Continued)

Able to migrate through embryonic Able to migrate through embryonic cellscells

Grow by invasionGrow by invasion Are euploid with 23 pairs of Are euploid with 23 pairs of

chromosomeschromosomes

Cancer DevelopmentCancer Development

Carcinogenesis/oncogenesis are Carcinogenesis/oncogenesis are names for cancer developmentnames for cancer development

Malignant transformation occurs Malignant transformation occurs through the following steps:through the following steps: InitiationInitiation PromotionPromotion ProgressionProgression MetastasisMetastasis

MetastasisMetastasis Metastasis occurs through a Metastasis occurs through a

progression of steps:progression of steps: Extension into surrounding tissuesExtension into surrounding tissues Blood vessel penetrationBlood vessel penetration Release of tumor cellsRelease of tumor cells InvasionInvasion Local seedingLocal seeding Bloodborne metastasisBloodborne metastasis Lymphatic spreadLymphatic spread

Cancer ClassificationCancer Classification Cancer grading and staging help Cancer grading and staging help

standardize diagnosis and treatment standardize diagnosis and treatment prognosis.prognosis.

Grading on the basis of cell appearance Grading on the basis of cell appearance and activity compares the cancer cell and activity compares the cancer cell with its normal parent tissue.with its normal parent tissue.

(Continued)(Continued)

Cancer Classification Cancer Classification (Continued)(Continued)

Staging classifies clinical aspects of Staging classifies clinical aspects of the cancer and determines exact the cancer and determines exact location and degree of metastasis at location and degree of metastasis at diagnosis.diagnosis.

Cancer Development Cancer Development

Oncogene activationOncogene activation Chemical carcinogenesis, physical Chemical carcinogenesis, physical

carcinogenesis, radiation, chronic carcinogenesis, radiation, chronic irritation, vital carcinogenesisirritation, vital carcinogenesis

Dietary factorsDietary factors Personal factors, immune function, Personal factors, immune function,

age, and genetic riskage, and genetic risk

Cancer PreventionCancer Prevention

Avoidance of known or potential Avoidance of known or potential carcinogenscarcinogens

Modification of associated factorsModification of associated factors Removal of “at-risk” tissuesRemoval of “at-risk” tissues ChemopreventionChemoprevention Screening programsScreening programs Gene therapyGene therapy