Cell Adhesion and the Extracellular Matrix Flashcards
What is the extracellular matrix ?
The environment surrounding cells, which varies between tissues.
What are the 3 major molecules involved in the ECM ?
Adhesive proteins
Structural proteins
Proteoglycans
Adhesive proteins
Adhere cells together
e.g. cadherins, integrins
Structural proteins
Gives tissues tensile, compressive strength.
- Collagen
- Elastin
- Keratin
Collagen function
Resists tension and can stretch
Elastin function
Elastic, returns tissue back to its original shape.
Keratin function
Tough, found in hair and nails
Proteoglycans
Fills space between cells, hydrates and cushions cells.
Consists of a protein core with sugar chains
Has a glue like function
How is collagen produced ?
Procollagen
Tropocollagen
Collagen fibrils
Collagen fibre
What is the loose connective tissues beneath the basement membrane of the epithelia majorly composed of ?
The ECM where fibroblasts are distributed.
Fibroblasts
Synthesise and secrete fibrillar proteins - collagen & elastin, as well as proteoglycans that help maintain the cell structural framework.
What is the major structural protein of the ECM ?
Collagen
Characteristics of collagen
Made of triple helix
Glycine, Proline and Hydroxyproline
What are the 4 types of collagen ?
Type (1) - Bone, Skin, Tendon
Type (2) - Cartilage
Type (3) - Reticulin, Blood Vessels
Type (4) - Basement membrane
What is the most abundant form of collagen ?
Type 1, which is one of the fibril forming collagens
Type 4 collagen
Network forming collagen
Major constituent of the basal laminae
What is the difference between type 1 and 4 ?
Type 4 Gly-X-Y is disrupted by a non helical short sequence. This gives it more flexibility.
What do adhesion proteins form interactions between ?
Collagen and proteoglycans
Fibronectin
Main adhesion protein in connective tissues.
Made of 2 polypeptide chains
Laminin
Main distinct adhesion protein in basal laminae
Myofibroblasts
Bi-functional
1. Fibroblast like as they secrete collagen
2. Smooth muscle-like (synthesise actin, myosin and desmin)
Action of myo-fibroblasts
Proliferate
Secrete collagen - SCAFFOLD
Consolidate damaged area - FIBROUS SCAR
Contract
Adipocytes
White fat cells
Function of adipocytes
Insulation
Packing - energy store
Describe the molecular defect in Duchenne Muscular Dystrophy
DMD is caused by changes (mutations) of the DMD gene on the X chromosome.
Mutation of the DMD gene will result in absence of the dystrophin protein, leading to degeneration of muscle fibres.
The body can replace (regenerate) some muscle fibers, but over time more and more muscle fiber is lost.
Recent experimental approaches to attempt to correct defect in DMD
Experimental drug PTC 124 (ataluren)- thought to override premature stop signal mutation to produce normal dystrophin
What happens during cancer progression ?
During cancer progression, cells lose their original tissue contacts, move through the extracellular matrix (ECM), enter into the lymphatic and/or blood system, extravasate, and ultimately form new tumors.
Carcinoma in situ
Carcinoma in situ refers to a group of abnormal cells that have not spread from the location where they first formed.
Cancer progression initial stages
Tumour cells accumulate
Cells have not yet breached the basal lamina
Cells undergo epithelial to mesenchymal transition.
Cancer progression - micro-invasion
Cells convert to ‘mesenchymal cells’ and the expression of cadherins is reduced
Micro-invasion starts sided by INVADIPODIA.
Secretion of MMP’s
Basement membrane breached
In invading tumours, leading cells express integrins, promoting interaction with the ECM and non-epithelial cells.
Cancer progression to metastasis
Autocrine motility factors form tumour.
Angiogenesis factors
Entry into and through lymphatic and blood vessels.
Dissemination - metastatis
Metastasis
The process by which cancer cells spread to other parts of the body.
