Cancer. Source: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.4259. 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
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:
…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
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.
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,
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,
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
…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
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
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