Unit 3 Flashcards
What does organizes the cells into tissues do?
allows for more complex structures
What are the functions of the ECM?
- adhesive substances
- provides structure
- presents growth factors to their receptors
- sequesters and stores growth factors
- senses and transduces mechanical signals
What does the ecm functioning as an adhesive substance do?
- proteins embeded in 1 membrane have a protrusion to invade neighbor
- tracks to direct migratory cells
- concentration gradients
What does the ecm functioning as provides structure do?
- defines boundaries
- provides integrity and elasticity to developing organs
- can enzymatically degrade debri and clean up microenvironment
What does the ecm functioning to present gf to their receptors do?
- controls spatial distribution of ECM bound surface molecules
- facilitates cross talk between gf receptors and ecm receptors
What does the ecm functioning to sequestor and store gf do?
- allows spatio temporal regulation of factor releases
- organizes morphogen gradients
- mediates release of factors in presence of correct forces
What does the ecm functioning to sense and transduce mechanical signals do?
- defines mechanical properties for cell differentiation
- activates intracellular signaling through cell surface receptors
- engages cytoskeletal machinery and synergizes gf signaling
- responds to pressure
Do all cells have cell adhesion molecules?
no
What do integrins do?
- bind surfece of epitheleal cell with antibodies
- think IG
What happens if there is a lack of cadherins?
- can’t tell structure of anything/ unorganized
- cell still mitose
- no cohesive shape or adherence
What are the type of cell adhesion proteins?
- integrins
- selectins
- cadherins
What are adhesive junctions?
- will attach cell to cell or cell to ecm
- always space btwn cells (25nm)
- allows for chemical transduction by exposing receptors, paracellular path
- protein filaments
What are the tight junctions?
- no measureable space between cells
- stomach, bladder
- bladder has junctions for stretching (along with desmosomes)
What organs contain desmosomes?
uterus, lungs, skin, bladder
Where are gap junctions found?
- heart so it can contract as a unit
- has ions and electrical signals so each cell doesn’t need its own signal
What are elastin proteins?
- helps allow for stretching
- break down as you age
- then forms crosslinks for less stretchability
- made by covalent bonds by lysine
- more crosslinks = less stretchy
What is fibronectin?
- adhesive proteins
- many cancer cells can’t produce (gene turned off or mutated) to allow for easier metastasis
What are the steps to breaking through the ECM?
- mutation and uncontrolled growth
- loss of cell adhesion
- increased motility (no anchor)
- entry and survival in circulation (seed and soil)
- exit into new tissue
- eventual colonization of new site
What are the requirements for metastasis?
- aggressive phenotype
- prereqs
- microenvironment
- intravasation
- life in transit
- distant accomplices
- homing
- extravasation
- micrometastasis
- co-opted stroma
- full colonization
What is an agressive phenotype?
oncogenic mutations, epigenic instability
What is are the metasis prereqs?
self-renewal
invasiveness
motility
detachment
survival
What is the metasis microenvironment?
- angiogenesis
- inflammation
- cancerized stroma
What is intravasion requirements?
epitheleal mesenchymal transitions
What is life in transit?
- platelet association
- embolism
- vascular adhesion
What are distance accomplices?
- vascular progenitors
- metastatic precursors
What is homing?
- attachment and attraction to survival signals
What does extravasation require?
- motility
- vascular remodeling
What is micro-metastasis?
- survival in dormancy
What is required for a co-opted stroma?
- angiogenesis
- inflammation
- cancerized stroma
What is required for full colonization?
- organ specific metastasis factors and functions
What are the pressures driving metastasis?
- hypoxia
- increased ROS (reductive oxidative species)
- decrease PH
- decreased LOX
How does hypoxia increase metastasis?
- HIF1 increase increases glycolysis and lactate transport
- could also increase acidity to degrade ECM proteins
How does increased reactive oxidative species increase metastasis?
would interfere with glycolysis through NADH
How does decreased LOX increase metastasis?
- H1F1 target
- decreased lox will decreae collagen fibrils in number and strength which will then decrease cell adhesion
- lox and h1f1 are directly proportional
- lox accelerates gross links makes it more rigid
Does LOX increase or decrease in cancer cells?
- in some tumors its increased in some its decreased
- can be increased and decreased cyclicly within the same cell
What guides cell motility?
- collagen alignment and the ECM
- ecm remodels and collagen increases in number and rigidity
- contains mutated fibroblasts
- forms pathway for cells to get to blood vessels
What do MMPs do in metastasis?
- facilitate breakdown of ECM
- requires ZN2+ or Ca2+ to work
- key regulator of tumor growth at primary and metastatic sites
- could exhbit pro or anti=apoptotic signals
- once tumor cell enters the blood stream, mmps can help break down epitheleal cells of blood vessels
How are MMPS regulators of tumor growth?
- tumor must break through ECM to go anywhere
How do MMPS facilitate the breakdown of the ECM?
- guides re-organization
Why are MMPS pro-metastatic and anti-metastatic ?
- pro apoptotic when it has somewhere to go
- anti-metastatic when primary site has plenty of room for growth or if there are no nearby blood vessels
How do MMPs help metastasis with blood vessels
helps start the process of angiogenesis if they detect there are no nearby blood vessels
How can MMPs be used as a cancer cure?
- cancer marker for detection
- drug target
What is an example of mmps in cancer?
- contact with omentum increases mmp transcription, protein expression, activation, secretion in ovarion
- proteins break down epithelial cells
- pieces of broken protein fibers allows for an increase of adhesion using integrins
