Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Disease and Defense > Invasion and Metastasis > Flashcards

Invasion and Metastasis Flashcards

1
Q

Do benign tumor invade?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

do benign tumors metastasize?

A

no

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

invasion

A

the infiltration of adjacent tissue by malignant cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

metastasis

A

the transfer of malignant cells from the primary site to a non-connected (secondary) site. So metastases are tumors discontinuous with the primary tumor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

in situ

A

epithelial cancers that display the cytologicla features of maligancy without invasion of the bm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

demarcation of malignant tumors?

A

malignant tumors are poorly demarcated from the surrounding normal tissue. Tumor protruding into surrounding tissue in a crablike fashion - hence the name cancer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

methods of cancer dissemination - 3 pathways

A
  1. direct seeding of body cavities or surfaces (e.g. ovarian)
  2. lymphatic
  3. hematogenous
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

the metastatic cascade (4)

A

invasion through BM and ECM

Intravasation - getting into blood / lymph

Extravasation - getting out of vessel at new site

Colonization - ability to grow at new site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why do cancer cells metastasize?

A

in the primary tumor, it becomes advantageous to move beyond the BM when conditions get crowded and harsh and hypoxia limits blood and nutrients - then there is a selective pressure to move out or metastasize

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

emerging hallmarks (nextgen) of cancer (4)

A

deregulation of cellular energetics (modify metabolism)

evade immunological destruction

tumor promoting inflammation

genome instability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

strong positive relationship between primary tumor size and

A

risk of developing metastasis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

intravasation

A

gaining access to the circulation by penetrating the vascular BM

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Invasion of the ECM is an active process that can be resolved into 4 steps

A
  1. changes “loosening” of tumor cell-cell interactions (e-cadherin loss)
  2. degradation of ECM
  3. Attachment to ECM components
  4. migration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What happens when tumor cells reach distant site?

A

extravasate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Step 1 in invasion -

A

dissociation of cell from one another - alterations in adhesion molecules (E-Cadherin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what links e-cadherins to cytoskeletin?

A

catenins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

after dissociation of cells from each other, what is the next step in invasion?

A

local degradation of the BM and interstitial CT

- Tumor cells secrete MMPs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How do MMPs regulate tumor invasion? (2)

A
  1. remodeling insoluble components of the basement membrane
  2. releasing ECM sequestering growth factors - cleavage products of collagen and proteoglycans have chemotactic, angiogenic, and growth promoting effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

In addition to degradation of ECM by MMP, what is another mode of invasion for cancer cells?

A

In vivo imaging shows that tumor cells can adopt a 2nd mode of invasion, termed ameboid migration - in which cells squeeze through spaces in teh matrix instead of cutting through it (using proteases)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

amoeboid migration -
speed?
railways?

A

quicker

collagen fibers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

why might amoboid movement explain the disappointing performance of MMP inibitors in clinical trials?

A

tumor cells can switch between the two forms of migration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

once the tumor cells have detached and degraded the BM, what happens next?

A

step 3 = changes in attachment of the tumor cells to ECM proteins

–> normal epithelial cells have receptors, such as integrins, for BM laminin and collagens that are at their basal surface; these receptors help to maintain the cells in a resting, differentiated state - loss of adhesion in normal cells leads to induction of apoptosis (anoikis or death by detachment)
No surprisingly, tumor cells are resistant to this form of death

Additionally, the matrix itself is modified in ways that promote invasion and metastasis - for example, cleavage of the BM proteins collagen IV and laminin by MMP2 and 9 generate novel sites that bind to receptors on tumor cells and stimulate migration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The last step in invasion (after the tumor cells have loosened, secreted ECM degradation shit, and loosened their attachment to the ECM) what happens?

A

LOCOMOTION
propels tumor cells through the degraded BM and zones of matrix proteolysis - migration is a complex, multistep process involving families of receptors and signaling proteins that impinge on the actin cytoskeleton

cells must attach to the matrix at the leading edge, detach from teh matrix at the trailing edge, and contract the actin cytoskeleton to ratchet forward

24
Q

Tumor cell movements?

A

movement can be potenitated and directed by tumor cell-derived cytokines
in addition, cleavage products of matrix components (collagen, laminin) and some GFs have chemotatic activity for tumor cells
proteolytic cleavage can liberate GFs bound to matrix molecules
stromal cells also produce paracrine effectors of cell motility

25
Q

Loss of E-cadherin is often associated with invasive phenotype - 4 ways E-cadherin expression can be lost

A
  1. LOH
  2. Inactivating mutation
  3. silencing via hypermethylation
  4. transcriptional repressors
26
Q

Transcriptional factors SNAIL, TWIST, and ZEB1/2 promote epithelial to mesenchymal transition (EMT) by?

A

repressing E-cadherin

27
Q

by repressing E-cadherin, transcriptional factors SNAIL, TWIST, and ZEB1/2 do what?

A

promote epithelial to mesenchymal transition

28
Q

What happens to E-Cadherin when ZEB1 is expressed?

A

it is repressed

29
Q

Is epithelial to mesenchymal transition normal?

A

Not in adult,

it is a normal process during development that gets used inappropriately by cancer cells

30
Q

Where in the metastatic cascade is the epithelial to mesenchymal transition thought to be necessary?

A

when they are intravasating and travelling through the circulation - can re-establish epithelial type characteristic upon recolonization

31
Q

Change associated with EMT
Upregulation?
Downregulation?

A

UP = mesenchymal proteins

DOWN = epithelial proteins (E-cadherin / cytokeratins)

32
Q

Do all EMT changes always occur and are they reversible

A

no they don’t all always occur and yes they are reversible

33
Q

What markers do circulating tumor cells express?

A

you can see that they become more mesenchymal - the more mesenchymal markers usually worse outcome

34
Q

What elements of the tumor microenvironment influence tumorigenesis? (3)

A
  1. mesoderm derived cells
    - fibroblasts
    - adipocytes
    - immune cells
    - endothelial cells
  2. ECM
    - collagen, etc.
  3. Soluble and matrix associated growth factors, cytokines, proteases
35
Q

what are tumor associated fibroblasts?

A

fibroblasts that exhibit altered expression of ECM molecules, proteases, protease inhibitors, and various growth factors

36
Q

once in the circulation, tumor cells are vulnerable to destruction by (3)

A
  1. mechanical shear stress
  2. apoptosis stimulated by loss of adhesion (anoikis)
  3. immune defenses
37
Q

anoikis

A

apoptosis stimulated by loss of adhesion

38
Q

what may enhance tumor cell survival in circulation?

A

in the circulation, tumor cells can aggregate in clumps. Adhesion between tumor cells and blood cells, particularly platelets, may enhance tumor cell survival and implantability -

39
Q

how can tuor cells cause emboli?

A

tumor cells can bind activate coagulation factors - resulting in the formation of emboli

40
Q

macrophages and tumor cell intravasation?

A

macrophages can actually assist tumor cells in intravasation (getting into the vessels)

41
Q

Extravasation -

A

site at which circulating tumor cells leave the capillaries can be due to the anatomic location of the primary tumor (1st capillary bed available) However, the natural pathways of drainage do not fully explain the distribution of metastasis

42
Q

Where does prostate cancer preferentially spread to?

A

bone - which is not first capillary bed

43
Q

Where do bronchogenic carcinomas tend to spread?

A

adrenals and brain

44
Q

where do neuroblastomas tend to spread?

A

live and bones

45
Q

two main theories to explain organ tropism of cancer metastatis?

A
  1. seed and soil

2. mechanical arrest

46
Q

seed and soil theory of organ tropism

A

explained by needs of cancer cell (seed) for a specific environment (soil) to initiate and maintain growth

47
Q

Ewing’s mechanical arrest theory

A

proposed that cells mechanically arrest in teh first capillary bed first encountered

48
Q

first step in extravasation?

A

adhesion to the endothelium - tumor cells express adhesion molecules and the endothelial cells of the target organ express ligands for the adhesion molecules -

49
Q

chemokines role in extravasation?

A

cancer cells can express chemokine receptors and the tissues that the cancer cells metastasize to express the chemokine - some target organs may liberate chemoattractants that recruit tumor cells to the site such as IGF1 and 2

50
Q

example of well vascularized tissue that is unfavorable for metastasis?

A

skeletal muscle

51
Q

are tumor cells efficient in colonizing distant organs?

A

no

52
Q

dormancy ??

A

prolonged survival of micrometastases without progression - is well described in melanoma and breast / prostate cancer

53
Q

pattern of colonization?

A

tumor cells secrete cytokines, growth factors, and ECM molecules that act on stromal cells, which in turn make the metastatic site habitable for the cancer cell

54
Q

ultmate effect of metastases?

direct?

A

invasive masses which interefere with normal fx

55
Q

ultimate effect of metastases?

indirect?

A

paraneoplastic syndrome - paracrine/endocrine effects occur in 7-15% of patients with cancer

56
Q

Causes of death (top 5)

A 
infection 
organ failure
thromboembolism 
hemorrhage 
emaciation

Disease and Defense (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions