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Year 1- Principles of Disease (FOM) > Invasive Cancer > Flashcards

Invasive Cancer Flashcards

1
Q

How are organs defined?

A

By basement membranes.

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2
Q

What are basement membranes made up of?

A

Extracellular matrix proteins- laminins, collagen and proteoglycans

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3
Q

What is the extracellular matrix?

A

Complete meshwork of proteins and carbohydrates

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4
Q

What does collagen/ proteoglycans provide the ECM with?

A

Structural integrity to tissues.

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5
Q

How is the ECM connected to other cells?

A

Directly connected to cells it surrounds- acts as an interface between cells and other structures like blood vessels.

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6
Q

How can cancer cells move into the bloodstream and then around the body>T

A

By penetration of the ECM

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7
Q

What are cadherins?

A

Type of cell adhesion molecule which bind to each other and the ECM

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8
Q

What is E-cadherin involved in?

A

Cell-cell adhesion of epithelial cells.

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9
Q

What do epithelial cancers often show?

A

Downregulation and mutation of E-cadherin.

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10
Q

What is the mechanisms of metasisis?

A

Tumour cells spread from the primary tumour.
This is subclonal meaning that the cells are genetically identical but differ by mutations.

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11
Q

Name the two different mechanisms used by metastasis.

A

Monoclonal
Polyclonal

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12
Q

Name the two different patterns used by metastasis.

A

Linear
Branched

->this gives different mutations

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13
Q

In order for cancer cell to spread, what must they beomce?

A

Must become mobile

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14
Q

What is epithelial mesenchymal transition (EMT)?

A

Conversion of closely connect epithelium cells to independent mesenchymal cells with the ability to move and invade their local environemnt.

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15
Q

Is the process of EMT reversible?

A

Yes

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16
Q

Where does EMT occur?

A

-Usually in embryogenesis but also occurs in cancer metastasis.

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17
Q

What are the five major steps that cells undergo in order to reach metastasis>

A
  1. Invasion
  2. Intravasation
  3. Transport
  4. Extravasation
  5. Colonisation
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18
Q

Do all cells found it the primary tumour have the ability to metasisise?

A

No

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19
Q

Describe the process of invasion.

A

EMT begins with signals from tumour stroma (HGF, TGF-beta) which stimulates kinase receptors (EFGR) & triggers MAPK pathway

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20
Q

Name two cell adhesion molecules which help w invasion.

A

Cadherins ( calcium dependent transmembrane proteins) & Catenins (protein inducing gene expression)

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21
Q

What do integrins do?

A

Enable cells to “break free” becoming mobile by modifying the membrane distribution.

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22
Q

What do proteases do?

A

Make the pathway through ECM by the destruction of tissues.
Matrix Metalloproteins contribute to loss of cell junctions

23
Q

What can mutation within E-cadherin lead to?

A

Inadequate cell-cell adhesion and distortion of cell shape.

24
Q

Describe intravasation.

A

Entry into blood or lymphatics.
->Tumour cell attaches to stromal side of basement membrane
->MMPs and serin proteases help to degrade basement membrane
->Tumour cell passes between the endothelial cells and off into the
bloodstream (transendothelial migration)

25
Q

Describe transport.

A

Circulating tumour cells travelling in a way one system around the body.
They can travel as a single cell or within a group of platelets (emboli).
Certain cancer cells have favoured metastatic sites.

26
Q

What are tumours in the bloodstream referred to as?

A

Circulating tumour cells (CTC’s).

27
Q

What is the first pass organ?

A

The first organ on route which lies downstream from the primary tumour.

For example, lungs are the first organ down the pathway from the breast.

28
Q

Describe extravasation.

A
  • Exit of tumour cells from bloods vessels into distant tissues
  • Tumour cells become trapped in capillaries
  • Reverse of intravasation
29
Q

What is E-selectin and what does it do?

A

->Calcium dependent receptor
-> enables attachment of the cancer cell to the endothelium surface of blood vessels and passage through the endothelium (transendothelial migration).

30
Q

How is the point of metastasis determined?

A

By the point of extravasation but also the microenvironment.

31
Q

What must the environment be like to allow tumours to grow?

A

Environment must be favourable and create new blood vessels (angiogenesis) for nutrients and oxygen.

32
Q

What form do dormant cancer cells take up?

A

Micrometastases

33
Q

What is angiogenetic switch dependant on?

A

Inhibitors and inducors.

34
Q

List some anti - angiogenic factors

A

Angiostatin
Endostatin
Prolactin
Protein 53 (p53)
Thrombospondin 1 & 2

35
Q

Name some pro-angiogenic factors.

A

VEGF
Fibroblast growth factor
Hepatocyte growth factor
Epidermal growth factor
Platelet derived growth factor

36
Q

What are the majority of angiogenetic inducers?

A

Grwoth Fcators

37
Q

What are the majority of angiogenetic inducers?

A

Growth Factors

38
Q

Which angiogenetic inducer is the most important and induces angiogenesis?

A

VEGF

39
Q

Name the five members of the VEGF family

A

A
B
C
D
Placental growth factor

40
Q

Which member of the VEGF family is secreted by a large number of tumour cells?

A

VEGF-A

41
Q

How do the members of the VEGF family transmit their signals?

A

Via three VEGF receptors.

42
Q

How is VEGFR activated?

A

Must be phosphorylated.

43
Q

How can tumour cells promote angiogenesis?

A

They stimulate nearby cells to produce VEGF and in turn promote angiogenesis

44
Q

What is VEGFR1?

A

Inhibitory and regulates the mito VEGF-A available.

45
Q

What does VEGFR2 do?

A

Enables angiogenesis.

46
Q

What is VEGFR3 required for?

A

The formation of lymphatic vessels.

47
Q

What do angiogenic inhibitors do?

A

Help to regulate angiogenesis.

48
Q

What can plasminogen can be cleaved to release?

A

Angiostatin- angiogenic inhibitor

49
Q

What does endostatin do?

A

Blocks the MAPK pathway thus inhibiting gene expression.

50
Q

What is Concomitant resistance?

A

Enabling growth in distant metastases
->can be as a result of surgery which activates previously dormant cells.,

51
Q

What is the angiogenic switch controlled by?

A

Hypoxia

52
Q

How do tumours create a hypoxic environment?

A

By activating HIF1 alpha & beta subunit triggering VEGF.

53
Q

Name one drug which inhibits angiogenesis.

A

TKI Afatanib

Year 1- Principles of Disease (FOM) (40 decks)

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