3-metastasis

Question 1

steps of metastasis

Answer 1

1. invasion
2. intravasation
3. transport through circulation
4. extravasation
5. colonization

Question 2

intravasation

Answer 2

invasive cells penetrate the wall of the recruited vessel

Question 3

extravasation

Answer 3

leave the vessel

Question 4

the _______ is a critical player in invasion and metastasis

Answer 4

tumor microenvironment

Question 5

the tumor microenvironment secrete factors that allow tumor cells to undergo

Answer 5

epithelial to mesenchymal transition

Question 6

2 phases of metastasis

Answer 6

1. physical translocation to new site
2. colonization at new site

Question 7

2 major strategies for invasion

Answer 7

1. single cell dissemination
2. collective migration

Question 8

3 prerequisites for invasion

Answer 8

1. cooperation of neighboring cells
2. secretion of proteases to degrade ECM
3. epithelial to mesenchymal transition (ECM)

Question 9

how can tumor cells become invasive

Answer 9

1. alter their adhesion molecules and receptors
2. tumor cells secrete protease or factors that induce stromal cells to inc. expression and secretions of enzymes
3. induce stromal cells to secrete chemokines and motility stimulatory factors that promote tumor cell migration

Question 10

ecm degradation necessary for ____ and ___

Answer 10

invasion
migration

Question 11

why do carcinoma cells go through EMT

Answer 11

-allow epithelial cells to transiently change their phenotype and acquire mesenchymal-like properties

Question 12

what happens to epithelium during EMT

Answer 12

dissolution of tight junctions and adheren junctions and causes the cells to express mesenchymal markers and secrete proteases

Question 13

what mediates EMT

Answer 13

EMT-TFs that are also responsible for the ability of carcinoma cells to degrade ECM and exhibit enhanced motility

Question 14

EMT breaks

Answer 14

intracellular adhesions

Question 15

inflammatory cells provoke

Answer 15

EMT

Question 16

stromal cells contribute to induction of

Answer 16

EMT

Question 17

4 pathways that a tumor can metastasize

Answer 17

1. blood vessels
2. lymphatics
3. body cavities
4. transplantation

Question 18

angiogenesis

Answer 18

the process by which new blood vessels sprout from pre-existing capillaries

Question 19

angiogenesis facilitates

Answer 19

intravasation

Question 20

normal oxygen conditions, prolyl-hydroxylase promotes _______ and ________ of HIF-1a

Answer 20

ubiquitination
proteasomal degredation

Question 21

under hypoxic conditions, prolyl-hydroxylase is ______. HIF1a is _____

Answer 21

inactive
not degraded

Question 22

HIF-1a accumulates and _________

Answer 22

induces transcription of VEGF and other angiogenic factors

Question 23

early stage tumors are not yet vascularized because______

Answer 23

the BM keeps them separate from the underlying blood vessels

Question 24

once tumors breach BM, they are

Answer 24

vascularized

Question 25

angiogenic switch refers to the transition

Answer 25

from a poorly vascularized, pre malignant phenotype to a highly vascularized, malignant one

Question 26

factors that are responsible for "throwing" the switch

Answer 26

-angiogenic activators -inhibitors

Question 27

Tumor TME interactions promote ______

Answer 27

tumor angiogenesis

Question 28

tumor cells secrete VEGF and other factors that stimulate proliferation and migration of endothelial cells but they dont reach targets___

Answer 28

because they are sequestered by components of ECM

Question 29

VEGF does not have an effect until Matrix metalloproteinases ________

Answer 29

degrade ECM which release active VEGF

Question 30

What cells secrete MMPs

Answer 30

tumor associated macrophages and mast cells

Question 31

tumor cells secrete factors that ___________

Answer 31

recruit and activate macrophages and mast cells

Question 32

macrophages and mast cells secrete other factors that ___

Answer 32

work in combination with VEGF to promote angiogenesis

Question 33

tumor cells, local inflamm cells stimulate endothelial cell survival, activation, proliferation, and migration. ________ recruit _____ which _____

Answer 33

activated endothelial cells endothelial cell progenitor cells mature to provide additional endothelial cells for capillary sprouting

Question 34

tumor vasculature

Answer 34

structurally and functionally abnormal few pericytes leaky perfusion is variable

Question 35

factors that induce invasion and angiogenesis also promote

Answer 35

entry into lymphatics

Question 36

circulating tumor cells encounter hazards

Answer 36

-physical forces -hostile microenvironment -anchorage dependent -tagets for NKs

Question 37

circulating tumor cells arrest via :

Answer 37

1. mechanical entrapment 2. site specific arrest

Question 38

2 methods that tumor cells can exit

Answer 38

1. single cell extravasation 2. intravascular growth and vessel rupture

Question 39

once a tumor cell infiltrates secondary site, it has several fates:

Answer 39

1. die 2. survive in dormant state 3. micrometastasis 4. proliferation to form macro-metastasis

Question 40

what happens when tumor cells are arrested in the vessel

Answer 40

endothelial cells express cell adhesion molecules (CAMs) that interact with tumor cell surface molecules

Question 41

factors that affect the fate of metastatic colony

Answer 41

1. dormancy (lack of GFs) 2. rate of cell division 3. angiogenesis

Question 42

formation of pre-metastatic niche

Answer 42

-remodel ECM -activate resident fibroblasts -mobilize inflammatory cells from bone marrow

Question 43

secondary tumor increases in size

Answer 43

micrometastasis

Question 44

further growth and dev of the tumor (macrometastasis) requires

Answer 44

recruitment of blood vessels