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Cancer Biology > Mechanisms of Metastasis > Flashcards

Mechanisms of Metastasis Flashcards

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1
Q

describe the correlation between size of tumor and probability of metastasis

A

larger tumor diameter = larger probability of metastasis

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2
Q

what are the steps to metastasis

A
  1. migration
  2. intravasation
  3. transport
  4. extravasation
  5. metastatic colonization
  6. angiogenesis
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3
Q

list the steps of invasion-metastatic cascade

A
  1. breach of basement membrane
  2. intravasation into blood micro vessels
  3. transportation of cancer cells
  4. cells become trapped
  5. cells extravasate
  6. formation of dormant micro metastasis
  7. macro metastasis formation
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4
Q

metastatic cells travel first to the _____ then to the ____

A

heart
lungs

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5
Q

metastatic cells that arise in the GI tract go to the _____ 1st

A

liver

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6
Q

metastatic cells arising in the lung go to the __________________ and then potentially ______________.

A

right side if the heart

anywhere in the body

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7
Q

integrins regulate…

A
  • tumor cell proliferation
  • survival and migration
  • metastatic spread
  • response to chemo and radiation
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8
Q

what is the function of beta-1 integrins

A

enable attachment of advancing caner cells to the still intact ECM

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9
Q

why do most cancer cells get trapped in blood vessels

A

b/c they are 2x the size of erythrocytes and are not deformable

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10
Q

list the cascade of event of extravasation

A
  1. cell trapped in capillary
  2. formation of microthrombus
  3. cancer pushes endothelial cells exposing basement membrane
  4. microthrombus is dissolved by proteases
  5. proliferation in lumen of capillary
  6. invasion of surrounding tissues
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11
Q

how can micrometastasis be detected

A

by their display of characteristic cell markers

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12
Q

micrometastasis can form a

A

draining node

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13
Q

what is a draining node

A

node that is directly connected w/ primary tumor via lymphatic duct that drains into tissue where tumor originated

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14
Q

what is the characteristic of beta catenin in tumor cells

A

diffused in the core

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15
Q

what is the characteristic of beta catenin in invasive cells

A

found only at the nucleus

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16
Q

beta catenin focused in the nucleus of invasive cells indicates

A

facilitated EMT

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17
Q

MMPs stand for

A

matrix metalloproteases

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18
Q

list some of the functions of MMPs that aid in extravasation

A

degrading ECM
activate GFs

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19
Q

what cleaves collagen fibers

A

carcinoma cells & fibroblasts

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20
Q

what effect do MMPs inhibit

A

collagen fibers being cleaved

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21
Q

the presence of what increased the release of MMPs

A

macrophages

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22
Q

what is formed when membrane-bound MMPs initiate proteolysis and invade ECM

A

podosomes

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23
Q

list the steps in locomotion of cultured cells

Study These Flashcards
A
  • organization of actin filaments to extend lamellipodia & establish new focal contacts
  • stress fibers contract tailing edge where focal points are broken
24
Q

making/ breaking focal contacts depends on the

Study These Flashcards
A

modulation of affinities of integrins for ECM

25
what are lamellipodia
structure used for cell movement
26
lamellipodia function
polymerize actin filaments
27
keratocytes characteristics
1. found in stromal tissue 2. produce & secrete collagen 3. give skin flexibility/ durability 4. create filopodia
28
what is heregulin
ligand for erbB2 receptor family
29
heregulin causes
lamellipodium formation
30
what are filopodia
extensions from plasma membrane or from lamellipodia
31
filopodia are used to
seek out nutrients for movement
32
what is the function of the Rho family
control actin cytoskeleton and the formation of focal adhesions
33
activation of Rho stimulates...
formation of focal adhesion and stress fibers
34
injecting an activeform of Rac protein stimulates the formation of
1 enormous lamellipodium
35
injecting a GEF for Cdc42 protein induces
extension of hundreds of filopodia in all directions
36
what is also expressed in inflammatory breast cancer
RhoC
37
what happens to RhoC when introduced in weakly metastatic cells
they become highly metastatic
38
the increased # of draining nodes found in a cancer indicates
increased probability of metastatic cells
39
what is the sentinel node
the 1st lymph node that is infiltrated by metastasizing cells
40
what induces lymphangiogenesis
VEGF-C secretion
41
what is lymphangiogenesis
lymph production
42
what types of tumors do not normally metastasize to other parts of the body
brain tumors
43
proportion of metastasis depends on
the adaptations necessary for survival in new tissue
44
colon cancer almost immediately metastasizes in the
liver
45
where is the venous return of most tissues located
to the right side of the heart
46
spleen and gut drain directly to the
liver via the portal vein
47
bone metastasis requires
interfering w. function of osteoclasts & osteoblasts
48
the formation of what structures compromise bone integrity
metastatic osteolytic lesions
49
osteolytic metastasis is characterized by
osteolytic lesions causing marrow to be displaced by cancer cells
50
osteoblastic metastasis is characterized by
osteoblastic lesions w/ marrow displaced by mineralized bone
51
balance between bone formation and bone resorption depends on
signaling between osteoclasts and osteoblasts
52
increase RANKL secretion leads to
bone resorption
53
increased OPG secretion blocks
RANKL and new bone is laid down
54
describe the positive feedback loop of osteolytic metastasis
release of GFs causes cancer to release more PTHrP resulting in bone demineralization exposing ECM in bone
55
what are 2 secondary complications that were discussed
depression in post-op breast cancer patients causing tumor to establish in the bone chronic stress causing an increase in the production of RANKL
56
what does enhanced metastasis indicate
cancerous cells are able to produce more metastases over a prolonged period of time when compared to original cells

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