Cell adhesion and the ECM Flashcards
What makes up the ground substance
Amorphous components in the ECM
What is the ECM made up of
An intricate and complex network of structural proteins that surrounds and provide support to cells of connective tissues
What does the ECM mediate
- Organisation of cells into tissues
- Coordination of cellular function
- Proliferation and gene expression
What are fibroblasts
They synthesise and secrete fibrillar proteins - collagen, elastic and reticular fibre and the respective complex carbs that helps maintain the cell structural framework
What is collagen
It is the major structural protein of ECM and is the most abundant proteins in animal tissues. It is highly flexible with high tensile strength
What are the characteristics of collagen
- Made of triple helix
- The helix domain contains 3 repeat of amino acid sequence
- The ring structure in the amino acid provides stability for the helical conformation of the polypeptide chains
- Associated with the helix molecule are sugar groups joined to the hydroxylysyl residue hence collagen can be described as a glycoprotein
How are proline and lysine modified
In the RER to hydroxyproline and hydroxylysine
What is type IV collagen
It is a network-forming collagen and is the major constituent of basal laminae
What is the difference between type IV and type I collagen
The gly-X-Y repeats of type IV collagen are disrupted by a nonhelical short sequence. This gives more flexibility to type IV collagen compared to fibril-forming collagens
What is elastin
It is the principal component of elastic fibre and are crosslinked through covalent bond formation between the residue side chain of lysine
What do the network of cross-linked side chains of elastin provide
Rubber like properties - stretching under tension and retorting to original state in non-tension
What are the structural fibrous proteins in the ECM embedded in
Gels made from polysaccharides known as GAGs
What are GAGs
They are negatively charged polysaccharides and bind positively charged ions and equally traps water molecules forming hydrated gels. They provide mechanical support to ECM
What is proteoglycan
- Matrix support/cushioning/hydration
- Glue-like function
- Links between proteins of ECM and cell surface
What links the ECM to intracellular cytoskeleton
Collagen/proteoglycans bind fibronectin that links to integrins which themselves bind via adaptors to actin cytoskeleton
What are adhesion proteins
They play the linkage role between the components of the matrix and the linkage of the matrix to the cell surfaces. They form interaction between collagen and proteoglycans for matrix organisation
What is an example of an adhesion protein
Fibronectin
What is laminin
It is the main distinct adhesion protein in the basal laminae. Cross or T like in shape
What is myofibroblast
It is bifunctional:
- Fibroblast-like secrete collagen
- Smooth muscle-like synthesise actin, myosin and desmin
What does myofibroblast do during tissue damage
- Proliferate
- Secrete collagen
- Consolidate damaged area
- Contract reducing size of damaged area
What are granules of mast cells composed of
Basophils which store chemical substances known as mediators of inflammation
What do B-lymphocytes differentiate to
Plasma cells
What can plasma cells synthesise
Immunoglobulin or antibodies
What are macrophages
They are phagocytic cells derived from monocytes containing high levels of lysosomes
Describe the stages of cell adhesion in cancer
- Tumour cells accumulate
- Cells have not breached the basement membrane
- Carcinoma in situ
- Cells undergo epithelial to mesenchymal transition
Describe microinvasion
- Cells convert to “mesenchymal” cells and expression of cadherins reduced
- Microinvasion starts aided by actin-based protrusions called invadipodia
- Secretion of MMPs
- Basement membrane breached
- In invading tumours leading cells to express integrins promoting interaction with ECM and non-epithelial cells during movement
Describe the progression to metastasis
- Autocrine motility factors from tumour
- Angiogenesis factors
- Entry into and through lymphatic and blood vessels
- Dissemination - metastasis
