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Lecture 23 t Cancer
x There are as many cancers as there are cell types in our bodies
The Phenotype of Cancer Cells
x Cancer cells have many different types of abnormalities
1. Lost important controls over cell growth: (d) t NO contact inhibition****
a. Spread on pteri dish, form a monolayer (single layers of cells)
b. Layer of cells make contact with each other. If cel next to them, they will stop growing
c. Respect boundaries = contact inhibition
d. Inhibited upon contact with neighbouring cells
e. Tumour cells have lost this ability, they no longer have this contact inhibition phenotype
f. Although they can also form monlayer, they can grow on top of each other and form
foci structure (little foci, little clumps of cells that can grow on top of each other that
lost this contact inhibition)
g. Figure 16.4 t difference in normal cells and cancer cells
i. Dotted blue line: growth of normal cells in the absence of any growth factors
(proteins supplied in medium that we grow cells in, positive signal for them to
divide because you have a lot of stuff) t absence: they will barely survive
ii. Solid blue line: will survive, over time graph will plateau b/c those growth
factors are used up, unless you replenish the culture medium, growth factors
are gradually used up until they die off
iii. Cancer cells ξ€š}v[ξ‚šξ€ƒξ€ξ€‚ξ‚Œξ€žUξ€ƒξ‚šZξ€žΓ‡ξ€ƒξ€š}v[ξ‚šξ€ƒξ€ξ€‚ξ‚Œξ€žξ€ƒ(}ξ‚Œξ€ƒξ‚šZξ€žξ€ƒξ‚‰ξ‚Œξ€žξ‚ξ€žvξ€ξ€žξ€ƒ}(vÇPξ‚Œ}Γξ‚šZ(ξ€‚ξ€ξ‚š}ξ‚Œξ‚ξ€ƒ]v
order to replicate and survive
iv. Provide with growth factors, extra incentive to grwo better
v. Solid and dotted red line does not vary, neither of the lines ARE NOT
PLATEAUING (like blue lines) t ξ€š}v[ξ‚šξ€ƒξ‚Œξ€žξ‚ξ‚‰}vξ€šξ€ƒξ‚š}ξ€ƒξ‚‰ξ‚Œξ€žξ‚ξ€žvξ€ξ€žξ€ƒξ€‚vξ€šξ€ƒξ€‚ξ€ξ‚ξ€žvξ€ξ€žξ€ƒ}(
2. They can be immortal and readily grow on soft agar
a. Agar = cleaned plastic plates
b. Plastic good surface for cells to stand on
c. Cells produce cell adhesion molecules, lay down matrix protein on plastic surface to
provide them something to grip onto
d. Normal cells not grow on soft agar = nothing to hold onto
e. Cancer cells accumulate mutations give them ability to cling onto soft surfaces
f. ξ€˜}v[ξ‚šξ€ƒξ€ξ€‚ξ‚Œξ€žξ€ƒ](ξ€ƒξ€œξ€’Dv]ξ‚šξ€ƒξ€š}wn stably, additional proteins use to bind to soft surfaces
g. Small tumour is isolated, we can spread it out on soft agar and look for growth
3. They have a larger number of chromosomal defects often as a result of their inability to repair
a. Mutated several proteins that would normally help them fix DNA damage because of
exposure or toxin created during replication
b. Normally, mismatch would be corrected
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c. BUT within cancer cell, mismatched would be replicated in 2 daughter cells with a
mutation in its genome beξ€ξ€‚Β΅ξ‚ξ€žξ€ƒΓ‡}Β΅[Γ€ξ€žξ€ƒ(]ξ€žoξ€šξ€ƒξ‚š}}ξ‚Œξ‚Œξ€žξ€ξ‚šξ€žξ€šξ€ƒξ‚šZξ€žξ€ƒu]uξ€‚ξ‚šξ€Zξ€ƒξ€žξ‚Œξ‚Œ}ξ‚Œξ‚ξ€ƒoξ€žξ€‚ξ€šξ€ƒξ‚š}
chromosomal abnormalities in cancer cells
d. Figure 16.5 t Karyotype of a breast cancer cell line *******************
i. Chromosomes are funky looking
ii. Translocations are very common in cancer cells
4. Overcome tissue boundaries and invade neighbouring tissues. This ability of cancer cells allows
several cancers to spread throughout the body
5. They can induce blood vessels to grow between them (secrete protein to bring them nutrients
so they can grow faster than cells around them)
Cancer is a Genetic Disease
x vξ€ξ€žξ‚Œξ€ƒ]ξ‚ξ€ƒξ‚šZξ€žξ€ƒξ‚Œξ€žξ‚Β΅oξ‚šξ€ƒ}(¡uΒ΅oξ€‚ξ‚šξ€žξ€šξ€ƒuΒ΅ξ‚šξ€‚ξ‚š]}vξ‚ξ€ƒξ‚š}ξ€ƒξ€‚ξ€ƒξ€ξ€žoo[ξ‚ξ€ƒξ€˜EÆ ^uΒ΅oξ‚š]-Z]ξ‚š_ZÇ}ξ‚šZξ€žξ‚]ξ‚ξ‚Žξ‚Žξ‚Žξ‚Žξ‚Ž
x Not a single mutation, but accumulation of a vast number of other mutations that eventually
lead to cancer
x Mutations that lead to cancer happen sporadically (all of a sudden, out of the blue) in somatic
cells in a particular tissue
x Most common solid tumour (reflected in North American statistics)
o Epithelial tissues
o High rate of cell division ******
o Mutant in a gene that regulates cell cycles, cleaerly these are the tissues that are more
affected (higher rate of cell division), miisregulate them higher chances
The Development of Cancer
x Mutations destabilized cell cycle in some way
x Cell cycle going through more often
x Develop slight growth advantage over remaining cells in that tissue = precancerous or
x Acquire further somatic mutations within that cell with the growth advantage
x Given rise to a tumour (or their cell clones) with malignant properties, ability to move away
o ****take up residence in other parts of the body
o Transported by the bloodstream or the lymphatic system
o This is known as metastasis (taken root in different part of the body)
Start with a single cell with mutation (growth advantage) to become premalignant, become malignant
with further mutations, transported to other regions of the body where they can set up a whole new
x Figure C t growth advantage, lost contat inhibition, additional somatic mutation now they have
becom e malignant and use transport system to be transported to other tissues where they ca
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