external factors controlling behaviour of cancer cells Flashcards
define cell behaviour
the way cells interact with external environment, especially proliferative/motile responses
external influences detected by cells
chemical- hormones, G.F, ion conc, ECM, nutrients/gases physical- mechanical stress, temperature, and topography (layout of ECM)
what external factors effect cell proliferation
growth factors cell-cell adhesion cell-ECM adhesion
behaviour of cells in cultutes
cell SPREADING- its not passive or influenced by gravity, energy is required
what happens when two cells stuck to each other
cell in contact with ECM substratum spreads, the one on top doesn’t
DIAGRAM how cell-ECM adhesion influences cell proliferation
when G.F given, cell suspended in agar (ie no contact with ECM) don’ t grow, but when bound to to ECM, they proliferate, hence binding to ECM essential
DIAGRAM experiment of cell spreading- difference between multiple blobs vs one big blob, thus importance and what it’s called
if ECM (in this case fibronectin) arranged in multiple blobs, cell survives, but if ECM arranged in only one area, more likely to die- thus attachment to ECM important for CELL SURVIVAL ie ANCHORAGE DEPENDENCE
DIAGRAM the effect of the type of matrix on phenotype of cell, thus importance
in interstitial matrix eg type 1 collagen, cells DON’T form secretory cells, rather just a ball of cells in basement membrane matrix, they form ORGANOIDS and are secretory shows cells sense composition of environment based on adhesion to ECM
cell-ECM adhesion molecules
cells have receptors which bind to ECM molecules, and are linked interiorly to cytoskeleton ie continuity between ECM and interior of cell
DIAGRAM structure of integrins
COMPLEX of alpha and beta subunits, which have heads (where ligand binding occurs) and tails (span plasma membrane)
what do integrins do with example
bind to short peptide sequences on ECM proteins eg binds to RGD, which is found in fibronectin for example
DIAGRAM what integrins form and thus their function
integrins CLUSTER to form focal adhesion OR hemidesmosomes, which are needed for SIGNAL transduction ie produce signal inside cell, called OUTSIDE-IN integrin signalling: do this by recruiting proteins eg focal adhesion kinase and assembly of actin
DIAGRAM different shapes in integrin signalling, and what determines this
can either be flexed or extended, which have different properties- determined by the composition of the ECM that it binds to
DIAGRAM other type of integrin signalling with examples
signal generated INSIDE cell eg hormone binds to other receptor, causing inactive integrin receptor ie low affinity (bent) to become active ie high affinity (extended) aka INSIDE-OUT integrin signalling once this occurs, OUTSIDE-IN signalling can then occur (integrin complex is extended) inflammation, clotting
DIAGRAM cells in culture
they proliferate to form a monolayer, then they stop proliferating this is NOT due to contact inhibition, but rather there is not enough growth factor ie DENSITY DEPENDENCE OF CELL DIVISION
DIAGRAM what controls cell proliferation
not just growth factor (density dependence of cell division) but also ECM (anchorage dependence), so BOTH are needed, and BOTH can activate the MAPK cascade
DIAGRAM contact-induced spreading of epithelial cells
when epithelial cells are in contact, they get bigger and spread, and their total area gets bigger= STABLE MONOLAYER
DIAGRAM adherens junction
cadherin on CSM is a Ca2+ dependent adhesion molecule, which is linked to cytoskeleton by beta and alpha catenin intracellularly
DIAGRAM roles of beta catenin
normally bound to cadherin to form stable adherens junctions if not bound, it’s in cytoplasm and is either broken down by active APC complex, or if APC complex inactive, it binds to LEF-1, and acts a T.F for cell proliferation
