Cell Adhesion and the Extracellular Matrix

Question 1

What is the extracellular matrix ?

Answer 1

The environment surrounding cells, which varies between tissues.

Question 2

What are the 3 major molecules involved in the ECM ?

Answer 2

Adhesive proteins
Structural proteins
Proteoglycans

Question 3

Adhesive proteins

Answer 3

Adhere cells together
e.g. cadherins, integrins

Question 4

Structural proteins

Answer 4

Gives tissues tensile, compressive strength.
- Collagen
- Elastin
- Keratin

Question 5

Collagen function

Answer 5

Resists tension and can stretch

Question 6

Elastin function

Answer 6

Elastic, returns tissue back to its original shape.

Question 7

Keratin function

Answer 7

Tough, found in hair and nails

Question 8

Proteoglycans

Answer 8

Fills space between cells, hydrates and cushions cells.
Consists of a protein core with sugar chains
Has a glue like function

Question 9

How is collagen produced ?

Answer 9

Procollagen
Tropocollagen
Collagen fibrils
Collagen fibre

Question 10

What is the loose connective tissues beneath the basement membrane of the epithelia majorly composed of ?

Answer 10

The ECM where fibroblasts are distributed.

Question 11

Fibroblasts

Answer 11

Synthesise and secrete fibrillar proteins - collagen & elastin, as well as proteoglycans that help maintain the cell structural framework.

Question 12

What is the major structural protein of the ECM ?

Answer 12

Collagen

Question 13

Characteristics of collagen

Answer 13

Made of triple helix
Glycine, Proline and Hydroxyproline

Question 14

What are the 4 types of collagen ?

Answer 14

Type (1) - Bone, Skin, Tendon
Type (2) - Cartilage
Type (3) - Reticulin, Blood Vessels
Type (4) - Basement membrane

Question 15

What is the most abundant form of collagen ?

Answer 15

Type 1, which is one of the fibril forming collagens

Question 16

Type 4 collagen

Answer 16

Network forming collagen
Major constituent of the basal laminae

Question 17

What is the difference between type 1 and 4 ?

Answer 17

Type 4 Gly-X-Y is disrupted by a non helical short sequence. This gives it more flexibility.

Question 18

What do adhesion proteins form interactions between ?

Answer 18

Collagen and proteoglycans

Question 19

Fibronectin

Answer 19

Main adhesion protein in connective tissues.
Made of 2 polypeptide chains

Question 20

Laminin

Answer 20

Main distinct adhesion protein in basal laminae

Question 21

Myofibroblasts

Answer 21

Bi-functional
1. Fibroblast like as they secrete collagen
2. Smooth muscle-like (synthesise actin, myosin and desmin)

Question 22

Action of myo-fibroblasts

Answer 22

Proliferate
Secrete collagen - SCAFFOLD
Consolidate damaged area - FIBROUS SCAR
Contract

Question 23

Adipocytes

Answer 23

White fat cells

Question 24

Function of adipocytes

Answer 24

Insulation
Packing - energy store

Question 25

Describe the molecular defect in Duchenne Muscular Dystrophy

Answer 25

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.

Question 26

Recent experimental approaches to attempt to correct defect in DMD

Answer 26

Experimental drug PTC 124 (ataluren)- thought to override premature stop signal mutation to produce normal dystrophin

Question 27

What happens during cancer progression ?

Answer 27

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.

Question 28

Carcinoma in situ

Answer 28

Carcinoma in situ refers to a group of abnormal cells that have not spread from the location where they first formed.

Question 29

Cancer progression initial stages

Answer 29

Tumour cells accumulate Cells have not yet breached the basal lamina Cells undergo epithelial to mesenchymal transition.

Question 30

Cancer progression - micro-invasion

Answer 30

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.

Question 31

Cancer progression to metastasis

Answer 31

Autocrine motility factors form tumour. Angiogenesis factors Entry into and through lymphatic and blood vessels. Dissemination - metastatis

Question 32

Metastasis

Answer 32

The process by which cancer cells spread to other parts of the body.