Mechanisms of Metastasis Flashcards
describe the correlation between size of tumor and probability of metastasis
larger tumor diameter = larger probability of metastasis
what are the steps to metastasis
- migration
- intravasation
- transport
- extravasation
- metastatic colonization
- angiogenesis
list the steps of invasion-metastatic cascade
- breach of basement membrane
- intravasation into blood micro vessels
- transportation of cancer cells
- cells become trapped
- cells extravasate
- formation of dormant micro metastasis
- macro metastasis formation
metastatic cells travel first to the _____ then to the ____
heart
lungs
metastatic cells that arise in the GI tract go to the _____ 1st
liver
metastatic cells arising in the lung go to the __________________ and then potentially ______________.
right side if the heart
anywhere in the body
integrins regulate…
- tumor cell proliferation
- survival and migration
- metastatic spread
- response to chemo and radiation
what is the function of beta-1 integrins
enable attachment of advancing caner cells to the still intact ECM
why do most cancer cells get trapped in blood vessels
b/c they are 2x the size of erythrocytes and are not deformable
list the cascade of event of extravasation
- cell trapped in capillary
- formation of microthrombus
- cancer pushes endothelial cells exposing basement membrane
- microthrombus is dissolved by proteases
- proliferation in lumen of capillary
- invasion of surrounding tissues
how can micrometastasis be detected
by their display of characteristic cell markers
micrometastasis can form a
draining node
what is a draining node
node that is directly connected w/ primary tumor via lymphatic duct that drains into tissue where tumor originated
what is the characteristic of beta catenin in tumor cells
diffused in the core
what is the characteristic of beta catenin in invasive cells
found only at the nucleus
beta catenin focused in the nucleus of invasive cells indicates
facilitated EMT
MMPs stand for
matrix metalloproteases
list some of the functions of MMPs that aid in extravasation
degrading ECM
activate GFs
what cleaves collagen fibers
carcinoma cells & fibroblasts
what effect do MMPs inhibit
collagen fibers being cleaved
the presence of what increased the release of MMPs
macrophages
what is formed when membrane-bound MMPs initiate proteolysis and invade ECM
podosomes
list the steps in locomotion of cultured cells
- organization of actin filaments to extend lamellipodia & establish new focal contacts
- stress fibers contract tailing edge where focal points are broken
making/ breaking focal contacts depends on the
modulation of affinities of integrins for ECM
what are lamellipodia
structure used for cell movement
lamellipodia function
polymerize actin filaments
keratocytes characteristics
- found in stromal tissue
- produce & secrete collagen
- give skin flexibility/ durability
- create filopodia
what is heregulin
ligand for erbB2 receptor family
heregulin causes
lamellipodium formation
what are filopodia
extensions from plasma membrane or from lamellipodia
filopodia are used to
seek out nutrients
for movement
what is the function of the Rho family
control actin cytoskeleton and the formation of focal adhesions
activation of Rho stimulates…
formation of focal adhesion and stress fibers
injecting an activeform of Rac protein stimulates the formation of
1 enormous lamellipodium
injecting a GEF for Cdc42 protein induces
extension of hundreds of filopodia in all directions
what is also expressed in inflammatory breast cancer
RhoC
what happens to RhoC when introduced in weakly metastatic cells
they become highly metastatic
the increased # of draining nodes found in a cancer indicates
increased probability of metastatic cells
what is the sentinel node
the 1st lymph node that is infiltrated by metastasizing cells
what induces lymphangiogenesis
VEGF-C secretion
what is lymphangiogenesis
lymph production
what types of tumors do not normally metastasize to other parts of the body
brain tumors
proportion of metastasis depends on
the adaptations necessary for survival in new tissue
colon cancer almost immediately metastasizes in the
liver
where is the venous return of most tissues located
to the right side of the heart
spleen and gut drain directly to the
liver via the portal vein
bone metastasis requires
interfering w. function of osteoclasts & osteoblasts
the formation of what structures compromise bone integrity
metastatic osteolytic lesions
osteolytic metastasis is characterized by
osteolytic lesions causing marrow to be displaced by cancer cells
osteoblastic metastasis is characterized by
osteoblastic lesions w/ marrow displaced by mineralized bone
balance between bone formation and bone resorption depends on
signaling between osteoclasts and osteoblasts
increase RANKL secretion leads to
bone resorption
increased OPG secretion blocks
RANKL and new bone is laid down
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
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
what does enhanced metastasis indicate
cancerous cells are able to produce more metastases over a prolonged period of time when compared to original cells
