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Cancer. Source: The Cells of Multicellular Organisms operate according to ecological principles The multicellular organism is an ecosystem of individual cells, reproducing by cell division and organized into

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The Cells of Multicellular Organisms

operate according to ecological principles

The multicellular organism is an ecosystem of individual cells,

reproducing by cell division and organized into

collaborative tissues and organs

Ecological Processes at work:

…Cell births

…Cell deaths

…Cellular habitats

…Cellular territorial limitations

…Maintaining cellular population sizes

But what about applying natural selection

to the cells of multi-cellular organisms?

What happens when the cells in a multi-cellular organism operate

In a world owned by the principles of natural selection?

In a healthy multi-cellular organism

self-sacrifice (apoptosis)—

as opposed to

survival of the fittest—

is the rule.

But what if the rules of the cells emerged from natural selection,

then, competition and mutation among somatic cells.

All somatic cell lineages

are committed to die.

Somatic cells leave no progeny.

They dedicate their existence

to support of the germ cells.

The germ cells alone

have a chance of survival.

The body is a clone.

The genome of the somatic cells

is the same as that of the germ cells.

By their self-sacrifice

for the sake of the germ cells,

the somatic cells help to

propagate copies of their own genes.

Free-living bacteria compete to survive!

The cells of a multicellular organism

are committed to collaborate!

To coordinate their behavior,

the somatic cells send, receive, and

interpret an elaborate set of signals

that serve as social controls,

telling each of them how to act!

Each cell behaves in a

socially responsible manner,

resting, dividing, differentiating,

or dying as needed

for the good of the organism!

Molecular disturbances that upset this harmony

mean trouble for a multicellular society.

A human body has 1014 cells, billions of cells.

These cells experience mutations every day,

potentially disrupting the social controls.

A mutation may give one cell

a selective advantage,

allowing it to divide more vigorously

than its neighboring cells

…to become a founder

of a growing mutant clone

A mutation that gives rise to such ‘CELLfish’ behavior

can jeopardize the future of the whole organism.

If repeated rounds of mutation, competition,

and natural selection operate

within the population of somatic cells

…then the basic ingredients of cancer

spell a recipe of potential disaster.

Individual mutant clones of cells

prosper at the expense of their neighbors,

but in the end destroy the whole cellular society.

Cancer is a microevolutionary process.

The cancer process occurs

on a time scale of months or years

in a population of cells in the body,

and it depends on

the same principles of mutation

and natural selection

that govern the long-term

evolution of all living organisms.

Evolutionary Principles

  • reproduce in defiance of

  • the normal restraints on cell division and

  • (2) invade and colonize territories

  • normally reserved for other cells.

If an isolated abnormal cell

does not divide more than

its normal neighboring cells,

then it does no significant damage.

But if cell division is out of control,

it will give rise to a tumor,

or neoplasm—

a relentlessly growing mass

of abnormal cells.

If the neoplastic cells

remain clustered in a single mass,

the tumor is said to be benign.

A complete cure can be achieved

by surgically removing the mass.

A tumor is cancer, if it is malignant.

If its cells have acquired the ability

to invade surrounding tissue.

Invasiveness centers on the cells’

ability to break loose,

enter the bloodstream

or lymphatic vessels,

and form secondary tumors,

called metastases,

at other sites in the body.

Even when a cancer has metastasized,

its origins can usually be traced to

a single primary tumor,

arising in an identified organ

derived by cell division from a single cell

that has undergone some

heritable change to outgrow its neighbors.

A tumor contains about a billion cells or more

…initiated by genetic changes

cancer cells have similar DNA abnormalities

…chemical carcinogens

…ionizing radiations such as x-rays


An estimated 1016 cell divisions

take place in a normal human body

in the course of a lifetime

Every single gene is likely to

undergo mutation

on about 1010 separate occasions

in any individual human being

If a single mutation were enough

to convert a typical healthy cell

into a cancer cell

that proliferates without restraint,

we would not be viable organisms.

The genesis of a cancer

requires that several independent,

rare accidents occur

in the lineage of one cell

Cancer requires mutations

in many genes—ten or more

The incidence of leukemia

in Hiroshima and Nagasaki

did not show a marked rise

until about 5 years

after the explosion

of the atomic bombs

Industrial workers exposed

for a limited period to chemical carcinogens

do not usually develop the cancers characteristic

of their occupation until 10, 20, or even more years

after the exposure

Long incubation period,

the prospective cancer cells

undergo a succession of changes

Tumors grow in fits and starts,

as additional advantageous mutations arise

those cells becoming the dominant clone

in the developing lesion

Evolution of Cancer

  • the mutation rate, probability per gene

  • per unit time that any given member of the

  • population will undergo genetic change

  • (2) the number of individuals in the population

  • (3) the rate of reproduction, the average number

  • of generations of progeny produced per unit time

  • (4) the selective advantage of successful

  • mutant individuals, the ratio of the number

  • of surviving fertile progeny they produce

  • per unit time to the number of surviving

  • fertile progeny produced by nonmutant

  • individuals.

1. They disregard the external and internal signals

that regulate cell proliferation.2. They tend to avoid suicide by apoptosis.3. They circumvent programmed limitations

to proliferation, escaping replicative senescence

and avoiding differentiation.4. They are genetically unstable.5. They escape from their home tissues

(that is, they are invasive).6. They survive and proliferate in foreign sites

(that is, they metastasize).

The tissue and cell type classifies malignant cancers.

Adenocarcinoma - originates in glandular tissue

Blastoma–originates in embryonic tissue of organs

Carcinoma–originates in epithelial tissue

(i.e., tissue that lines organs and tubes)

Leukemia–originates in tissues that form blood cells

Lymphoma–originates in lymphatic tissue,

BCell, TCell proliferations lymphomas

Myeloma–originates in bone marrow, hemopoietic cells

Chondroma—tumors of the cartilage

Sarcoma–originates in connective or supportive tissue

(e.g., bone, cartilage, muscle)

90% of human cancers are carcinomas

Grading CancerUnder a microscope, examining tumor cells

obtained through biopsy

Abnormality determines the grade of the cancer,

increasing the grade, from 1 - 4.

Cells that are well differentiated

closely resemble mature, specialized cells.

Cells that are undifferentiated

are highly abnormal, immature and primitive.

Grade 1 Cells slightly abnormal and well differentiated

Grade 2 Cells more abnormal and moderately differentiated

Grade 3 Cells very abnormal and poorly differentiated

Grade 4 Cells immature and undifferentiated

Classify the extent of the cancer

Stage 0 Cancer in situ (limited to surface cells)

Stage I Cancer limited to the tissue of origin,

evidence of tumor growth

Stage II Limited local spread of cancerous cells

Stage III Extensive local and regional spread

Stage IV Distant metastasis

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