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Flashcards in Week 2 Deck (28):
1

What is metastasis?

Spread of tumour to- and growth at- ectopic sites, via blood, lymphatics, intra-epithelial route, or trans-coelomic

2

What is invasion?

Growth by infiltration and destruction of surrounding tissues

3

What is the tissue of origin of carcinoma?

Malignant tumour derived from epithelial cells

4

What is the tissue of origin of sarcoma?

Malignant tumours derived from mesenchymal cells

5

What is the tissue of origin of melanoma?

Malignant tumour derived from neural crest cells

6

What is the tissue of origin of leukaemia?

Malignant tumour derived from circulating WBCs

7

What is the tissue of origin of lymphoma?

Malignant tumour derived from lymphatic system

8

Describe the basement membrane (BM):

- delineates epithelial or endothelial tissues
- secreted by basal epithelial cells/endothelial cells
- a layer of extracellular matrix (ECM)
- fibronectin, type IV collagen, laminin, etc
- a barrier to spread (esp. carcinoma cells)

9

What events makes up the metastatic cascade?

local invasion -> neovascularisation/angiogenesis -> detachment -> intravasation (into blood or lymph) -> transport -> lodgement/arrest -> extravasation -> growth at ectopic site -> local invasion

10

What are the main properties of metastatic tumour cells?

1. reduced cell-cell adhesion
2. altered cell-substratum adhesion
3. increased motility
4. increased proteolytic ability
5. angiogenic ability
6. ability to intravasate and extravasate
7. ability to proliferate (locally and in ectopic sites)

1-4 common to invasion and metastasis, 5-7 specific to metastasis

11

What must be disrupted for cell-cell adhesion to be broken?

E-cadherin (e-CD) in adherens junctions

12

How does cell-cell adhesion occur?

Homotypic adhesion (ligand and receptor are same)- e-CD binds e-CD on adjacent cells (like a zip or a tent-peg)

13

What does e-CD attach to inside the cell?

alpha and beta catenin, and the actin-myosin cytoskeleton

14

What does e-CD require for adhesion?

Calcium (2+) in the extracellular space

15

What indirect mechanisms can disturb e-CD adhesion between cells?

Exon-skipping, methylation of e-CD promoter, mutations in proteins that interact with e-CD (beta-catenin, APC) and mutations in transcription factors that regulate e-CD (snail, slug, twist)

16

What are integrins?

- Cell adhesion molecules (CAMs), integral to plasma membrane, bind to ECM molecules
- Found in basal epithelial cells and in focal adhesions of migrating cells

17

What are the possible mechanisms of integrins in metastasis?

- decreased adhesion to BM surrounding epithelium
- increased migration through stroma
- increased adhesion to BM or endothelial cells of BVs
- binding site for proteolytic enzymes

18

What is HGF?

- Hepatic growth factor or 'scatter factor' can induce epithelial cells to dissociate and scatter in culture
- HGF is a mitogen (GF), a motogen (motility factor) and a morphogen

19

What cells are associated with the tumour microenvironment (TME)?

- Cancer-associated fibroblasts (CAFs)
- Immune cells that have infiltrated the tumour
- myofibroblasts
- tumour-associated vasculature
- pericytes
Secreting;
- GFs
- chemokines
- enzymes

20

What are the site-specific metastasis for breast tumours?

Bone, lungs, liver and brain

21

What are the site-specific metastasis for lung adenocarcinoma?

Brian, bones, adrenal gland, liver

22

What are the site-specific metastasis for skin melanoma?

Lungs, brain, skin, liver

23

What are the site-specific metastasis for colorectal tumours?

Liver and lungs

24

What are the site-specific metastasis for pancreatic tumours?

Liver and lungs

25

What are the site-specific metastasis for prostate tumours?

Bones

26

What are the site-specific metastasis for sarcoma tumours?

Lungs

27

What are the site-specific metastasis for uveal melanoma tumours?

Liver

28

What are some of the possible mechanisms for organ tropism?

- Selective adhesion to endothelium of target organs
- Selective response to GFs at ectopic site
- Selective migration to CK source
- Factors released by tumour/other cells cause changes in prospective TME at secondary sites, creating pre-metastatic niche
- Balance of local angiogenic factors versus systemic anti-angiogenic factors (angiostatin and endostatin)