Kate Angel 4 Flashcards
Why do cancer cells need to be motile?
This allows them to invade tissue and intravasate and extravasate
What are the effects of EGF and HGF on cancer cell motility?
HGF induces multidirectional movement of cells expressing the receptor
EGF can also induce cancer cell movement
What is the mechanism of cancer cell locomotion on solid substances?
The cell restructures its actin cytoskeleton to form filaments in the direction of movement leading to the formation of lamellipodia
The extension of the lamellipodia results in the formation of new focal contacts between the leading edge and the substrate
Stress fibres then contract the trailing edge of the cell breaking its focal contacts moving the cell foward
What forms the focal contact between the cell and ECM components?
Integrins with 24 heterodimers possible each binding to a particular molecule
What are integrins?
A family of heterodimeric proteins with an alpha and beta unit which cluster where their ligan is recognised forming a focal adhesion and influencing the structure of the actin cytoskeleton
What is the function of integrins?
They can stabilise/tether both normal and cancer cells in a tissue
This enables cells to gain traction through firm physical connections with the ECM
They are also capable of activating signalling pathways resulting in cell migration, proliferation and survival
What is the difference between filopodia and lamellipodia?
Lamellipodia are relatively large structures formed by bundles of actin while Filopodia are smaller structures formed by actin monomers which are added to as barbed ends and extend from the lamellipodia
What controls the actin cytoskeleton and formation of focal adhesions?
Rho family proteins which manage cell shape and motility
These are divided into three subfamilies Rho, Rac and Cdc42 proteins
Rho is belived to play a role in stress fibre formation
Rac is believed to play a role in lamellipodia formation
Cdc42 is believed to play a role in Filopodia formation
What is the relationship between growth factor receptors and Rho family members?
EGF can activate a number of rho proteins to stimulate cell motility with many downstream proteins responsible and all three subfamilies contributing to motility (the proportions of these families change during cancer)
How can lymphatics provide a way for dissemination of metastasing cancer cells?
Lymphatic vasculatire is found throughout all tissues with a structure designed for uptake of interstitial fluid and lipids etc allowing it to be transported back into the blood stream this structure is therefore relatively permeable compared to blood vasculature making it an easy target for tumour cells
These cells can then form metastasis in the lymph nodes however recent evidence suggests this may be a dead end for the cancer cell so most distant metastasis is due to blood dissemination
How is lymphatic vasculature remodelled in tumours?
The structure is unable to handle the pressure inside tumours and would collapse so unlike angiogenesis where blood vessels extend into the tumour, lymphatic vessels are increased around but not inside the tumour
What influences whether a cancer cell will seed and form a macromestasis in a tissue?
Both the circulation as this will control what tissues the cell is likely to encounter and may result in a cell colonizing a relatively inhospitable tissue simply due to the number of cells which encounter it
The tissue as it might not provide an environment which the cell can survive in
The adaptions of the cancer cell as evidence suggests that cancer cells become extremely specialized in order to colonize a specific tissue
What is the evolving view of the relationship between the primary tumour and metastasis?
The pre metastatic niche model where before tumour cells arrive tumour derived factors cause stem cells to be recruited to the secondary site where they can provide a more hospitable site for the cancer cell
The self-seeding model where the circulating cell finds the most appropriate region for colonization
How can sites which would normally be inhospitable become hospitable?
If a region becomes wounded or inflamed the immune cells can provide signals which support metastasis in areas where this would not normally occur
