cancer biology Flashcards
what external influences are detected by cells?
chemical
–>hormones, growth factors, ion concs, ECM, molecules on other cells, nutrients and dissolved gas (O2/CO2) concs.
physical
–> mechanical stresses, temperature, the topography or “layout” of the ECM and other cells
which external factors are most influential of cancer growth?
Growth factors
Cell-cell adhesion
Cell-ECM adhesion
how can cell to the ECM affect cell proliferation?
Cells require to be binding to extracellular matrix to be fully competent for responding to soluble growth factors
In suspension, cells do not significantly synthesise DNA or protein, the require to be attached to ECM (and a degree of spreading) to do this.
Attachment to the ECM may be required for survival – Anchorage Dependency.
o Cells have receptors on their surface for ECM molecules
- -> receptors are linked to the cytoskeleton inside the cell
- ->leading to a mechanical continuity between the ECM and the cytoplasm.
how do cells adhere to the ECM?
cells have receptors on their surface which bind specifically to the ECM molecules.
which is the most important matrix binding molecule? and describe
integrins
heterodimer complex of a and b subunits
ligand binding occurs at the junction of the head regions
both ‘leg’ subunits span the plasma membrane
how can integrins bind to multiple molecules?
~10 a and 8 b sub-units are known which can make >20 combinations.
what is “outside-in” intergrin signalling?
ECM receptors can act to transduce signals inside the cell when stimulated.
e.g. the composition of the ECM will determine which integrin complexes bind and which signals it receives
this can alter the phenotype of the cell
what is “inside-out” intergrin signalling?
a signal generated inside the cell (e.g. as the result of hormone binding to receptor) can act on an integrin complex to alter the affinity of an integrin (i.e. alter its affinity for its ECM binding)
e.g. in inflammation or blood-clotting, switching on adhesion of circulating leukocytes
what is density dependence of cell division
At high density, cells compete for growth factors and when cells form a confluent monolayer, they stop proliferating because the growth factors have been all used up.
–> This is a competing theory for contact inhibition – that when cells meet each other in a mono-layer, they stop proliferating due to the contact of the cells.
what are the different types of contact interactions between cells?
short-term: transient interactions between cells which do not form stable cell-cell junctions
long term: stable interactions resulting in formation of cell-cell junctions
what do junctions between cells depend on?
calcium
without calcium the cell cell junctions break down and there is high proliferation
what can beta catenin do?
o Rapidly degrade when bound to Adenomatous polyposis coli (APC).
o When at a high enough concentration, can bind to LEF-1 in the nucleus and alter gene transcription.
o Re-bind back onto cadherin (cannot have nuclear effects)
what is an oncogene?
mutant gene which promotes uncontrolled cell proliferation
what is a proto-oncogene?
normal cellular gene corresponding to the oncogene
how does a primary carcinoma cell metastasise?
cell-cell adhesion must be down-regulated (e.g. cadherin levels reduced)
the cells must be motile
degradation of ECM must take place; matrix metaloproteinase (MMP) levels increased in order to migrate through basal lamina and interstitial ECM
the degree of carcinoma cell-cell adhesion is an indicator of how differentiated the primary tumour is, and indicates its invasiveness and the prognosis
