carcinogenesis 2: external growth factors

Question 1

what is cell behaviour?

Answer 1

the way cells interact with their external environment and their reactions to this, particularly proliferative & motile responses

Question 2

what external influences are detected by cells?

Answer 2

CHEMICAL:

• hormones
• growth factors
• ion concentrations
• ECM
• molecules on other cells
• nutrients
• dissolved gas concs

PHYSICAL:

• mechanical stress
• temperature
• topography of ECM and other cells

Question 3

what external growth factors are important in influencing cell devision?

Answer 3

• growth factors
• cell-cell adhesion
• cell-ECM adhesion

Question 4

what happens when a cell settles on a matrix surface?

Answer 4

it settles

Question 5

how does cell-ECM adhesion affect proliferation?

Answer 5

increases chance

(- when cell suspended in agar chance of entereing s phase was 8%

• perched on small adhesive patch was 30%
• spread on a big adhesive patch was 90%)

Question 6

what is anchorage dependence?

Answer 6

cells require to be binding to ECM in order to respond properly to soluble growth factors

Question 7

does matrix type affect phenotypes of cells?

Answer 7

yes

(- experiments in 3D matrix gel cultures highlight differences
- In type 1 collagen gel cells mammary epithelium did not differentiate but in basal lamina matrix gel they did)

Question 8

what are integrins?

Answer 8

heterodimer complexes of α & β subunits with heads in ECM & tails in plasma membrane

• bind specifically to short peptide sequence on ECM proteins eg α5β1 fibronectin receptor binds arg-gly-asp (RGD)
• peptide sequences such as RGD are found in more than one ECM molecule

Question 9

how do integrins bind?

Answer 9

to actin microfilaments at focal adhesions

- except α6β4 complex (linked to intermediate filaments at hemidesmosomes)

Question 10

how can cell-ECM binding be switched on and off?

Answer 10

integrin complexes can adopt flexed and extended molecular fonrimations
- switching between these confirmations affects ability to bind to ligands & signalling

Question 11

what is outside-in signalling?

Answer 11

when ECM binds to integrins a signal is transmitted from outside the cell to the inside

Question 12

what is inside-out signalling?

Answer 12

signal generated inside cell acts on integrin complex to alter affinity of integrin MORE

Question 13

what does the amount of force generated at a focal adhesion depend on?

Answer 13

both the force generated by cytoskeleton & stiffness of ECM