LEC51: Properties of Cancer Cells; Senescence Flashcards Preview

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Flashcards in LEC51: Properties of Cancer Cells; Senescence Deck (26):
1

benign vs malignant

clinical terms 

benign: cells that're undergiong uncontrolled proliferation but that doesn't manifest in disease 

malignant: cells with unlimited cell renewal and result in what is generally considered to be cancer

2

primary cells?

cells w/ a finite lifespan, finite ability to grow, that are directly removed from the organism 

3

immortalized cells?

cells with unlimited life span, capable of growing indefinitely

4

transformed cells?

immortalized cells that've gained some (lab-measurable) properties, including anchorage-independency or failure to stop growing upon contact w/ other cells - properties make it resemble a cancer cell

5

tumorigenic cells?

transformed cells that have ability to form a tumor 

determine this by doing an assay for tumor formation

6

properties of cancer cells?

1) epithelial to mesenchymal morphology

2) altered metabolism 

3) unlimited cell renewal; are immortal

4) anchorage independent

5) proliferate even when in contact w/ other cells

6) grow independent of growth factors

7) changes in ploidy 

7

morphology of cancer cells?

changes from normal epithelial to mesenchymal, spindle-shaped, fibroblast cell type

appears refractile in light microscope due to cytoskeletal changes including actin depolymerization 

 

8

how is cancer cell metabolism altered? 

they rely on glycolysis for their ATP production, whereas normal cells use TCA cycle for ATP 

 

9

why do cancer cells rely on an inefficient form of ATP production for their energy?

1) cancer cells grow in hypoxic environment; get their oxygen from glycolysis; have intrinsic property of enhanced glycolytic rate

2) use TCA cycle components to make amino acids, ntds, fatty acids that cancer cells need to make more of themselves

 

10

what is cancer cells' potential?

unlimited

thus considered immortalized

11

how do normal vs cancer cells proliferate?

normal epithelial or mesenchymal cells require anchorage to proliferate; cancer cells are anchorage independent for growth b/c do not need to activate the ERK pathway, upregulate Cyclin D, in order to proliferate

12

what is "contact inhibition" re: normal vs. cancer cells?

epithelial cells are restrained in their growth when they come into contact with another cell 

cancer cells lose contact inhibition; so they proliferate even when they are touching adjacent cells

13

growth factors' importance to normal vs. cancer cells?

growth factors trigger the ERK pathway, lead to Cyclin D upregulation. normal cells need this for transcriptional upregulation of Cyclin D to enter cell cycle, divide 

cancer cells grow in a manner independent of growth factors b/c can upreglate ERK pathway independent of Cyclin D

14

how does retinoblastoma circumvent growth factors for its growth?

Rb normally prevents cell cycle progression by binding to E2F, preventing turning on of E2F target genes 

In retinoblastoma, a cell that mutates/loses Rb has an unrestrained E2F; so can do transcription absent of signaling 

 

15

what is cancer cell re: ploidy?

aneuploid, could be gain or loss of genetic material due to deletions, gene amplification, chromosomal translocation 

have something other than 4N 

16

what is metastasis?

cancer cells acquire ability to recruit blood vessels or cause angiogenesis in order to grow as a tumor 

to enter bloodstream, travel to distant sites within organism, tumor cells become invasive 

this ability to seed at distant sites is metastasis

17

what did fibroblasts growing in culture show?

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1) senescence: they were seen to have a finite life span, to stop proliferating after a certain period of time when they had depleted pRb and p53, and this was an M1 event, senescence

2) lacking telomerase: fibroblasts continued to proliferate after M1 until an M2 event or crisis, due to no telomerase expression, so stopped growing

restoration of telomerase expression allowed them to continue to grow indefinitely

 

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18

what is the appearance of senescent cells?

how are they visualizable?

huge, flat, "fried egg" look 

large cytoplasm 

they express an acidic form of Beta-galactosidase that's detectable at a low pH by using a colorimetric assay in which senescent cells stain blue 

bottom image is senescent fibroblast cells, top is normal fibroblasts

 

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19

what is the definition of senescence, vs. quiescence?

senescence: irreversible cell cycle arrest 

whereas quiescence: reversible cell cycle arrest 

 

20

what  causes replicative senescence?

telomere shortening

21

what is the basis of senescence re: telomere shortening?

telomeres protect chroosomes from being viewed by the cell as DNA damage, by forming a t-loop at the end of the chromosome 

with each round of replication, telomeres shorten, some DNA repeats are lost; eventually, becomes so short, cannot form a T loop

when telomeres shorten so much they cannot form t-loop, cell perceives DNA damage, activates p53 pathway -> senescence

22

when does p53 pathway get activated? what if it was lost?

p53 activated when telomeres shorten enough that they cannot form t-loops

cell perceives these as DNA damage, activates p53 pathway, which causes senescence

if p53 is deleted, cells continue to proliferate and telomeres continue to shorten; eventually, chromosomes lose coding regions, undergoes a crisis

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23

what causes premature senescence?

prolonged DNA damage or other forms of stress

cells can undergo senescence by activation of p53 by means other than telomere shortening 

stresses such as sustianed DNA damage that cannot be repaired, or activation of specific oncogene pathways, trigger p53-dependent senescence 

24

how can a cell exit a crisis re: telomeres?

reactivate telomerase 

25

how do cancer cells do telomere maintenance?

1) telomerase expression is re-activated; in most cells

2) ALT cells, a telomerase-independent method, do homologous recombination of telomeric DNA; in 10-20% of cells

26

how is ALT dependence shown experimentally?

ALT cell is proven if can show that a cell can exit a crisis even with a telomerase inhibitor added to culture, i.e. TERT

 

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