Cell adhesion and the ECM Flashcards

1
Q

What makes up the ground substance

A

Amorphous components in the ECM

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1
Q

What is the ECM made up of

A

An intricate and complex network of structural proteins that surrounds and provide support to cells of connective tissues

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2
Q

What does the ECM mediate

A
  • Organisation of cells into tissues
  • Coordination of cellular function
  • Proliferation and gene expression
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3
Q

What are fibroblasts

A

They synthesise and secrete fibrillar proteins - collagen, elastic and reticular fibre and the respective complex carbs that helps maintain the cell structural framework

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4
Q

What is collagen

A

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

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5
Q

What are the characteristics of collagen

A
  • 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
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6
Q

How are proline and lysine modified

A

In the RER to hydroxyproline and hydroxylysine

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7
Q

What is type IV collagen

A

It is a network-forming collagen and is the major constituent of basal laminae

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8
Q

What is the difference between type IV and type I collagen

A

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

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9
Q

What is elastin

A

It is the principal component of elastic fibre and are crosslinked through covalent bond formation between the residue side chain of lysine

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10
Q

What do the network of cross-linked side chains of elastin provide

A

Rubber like properties - stretching under tension and retorting to original state in non-tension

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11
Q

What are the structural fibrous proteins in the ECM embedded in

A

Gels made from polysaccharides known as GAGs

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12
Q

What are GAGs

A

They are negatively charged polysaccharides and bind positively charged ions and equally traps water molecules forming hydrated gels. They provide mechanical support to ECM

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13
Q

What is proteoglycan

A
  • Matrix support/cushioning/hydration
  • Glue-like function
  • Links between proteins of ECM and cell surface
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14
Q

What links the ECM to intracellular cytoskeleton

A

Collagen/proteoglycans bind fibronectin that links to integrins which themselves bind via adaptors to actin cytoskeleton

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15
Q

What are adhesion proteins

A

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

16
Q

What is an example of an adhesion protein

A

Fibronectin

17
Q

What is laminin

A

It is the main distinct adhesion protein in the basal laminae. Cross or T like in shape

18
Q

What is myofibroblast

A

It is bifunctional:
- Fibroblast-like secrete collagen
- Smooth muscle-like synthesise actin, myosin and desmin

19
Q

What does myofibroblast do during tissue damage

A
  • Proliferate
  • Secrete collagen
  • Consolidate damaged area
  • Contract reducing size of damaged area
20
Q

What are granules of mast cells composed of

A

Basophils which store chemical substances known as mediators of inflammation

21
Q

What do B-lymphocytes differentiate to

A

Plasma cells

22
Q

What can plasma cells synthesise

A

Immunoglobulin or antibodies

23
Q

What are macrophages

A

They are phagocytic cells derived from monocytes containing high levels of lysosomes

24
Q

Describe the stages of cell adhesion in cancer

A
  • Tumour cells accumulate
  • Cells have not breached the basement membrane
  • Carcinoma in situ
  • Cells undergo epithelial to mesenchymal transition
25
Q

Describe microinvasion

A
  • 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
26
Q

Describe the progression to metastasis

A
  • Autocrine motility factors from tumour
  • Angiogenesis factors
  • Entry into and through lymphatic and blood vessels
  • Dissemination - metastasis