Invasion and Metastasis Flashcards
(29 cards)
are mets a good or bad prognostic indicator
bad
90% cancer deaths caused by mets
what is the most influencial thing determining where a cancers mets to
the primary tumour type
are the mets the same type of cancer as the primary tumour
yes
but may have some different mutations
what are pioneer cells
are spawned form primary tumours, invade adjacent tissues and travel to new sites
what is the role of metastasise
to colonise new areas where oxygen and nutrients are not limiting
what are the 5 major steps in metastasis
invasion and infiltration of surrounding tissues with penetration of small lymph/ vascular channels (intravasation)
release of neoplastic cells (single, in clumps)
survival in circulation
arrest in the capillary beds of distant organs
penetration of vessels (extravasation), growth of tumour in new site (micromestasis -> colonisation -> macrometastasis)
how do cancer cells intravasate
undergo EMT
allows change in shape and motility= increased ability to disrupt BM
what is the MET
mesenchymal to epithelial transition
reverse of EMT following extravasation at secondary site to enable cancer cells to re-establish
what changes in the EMT
loss of cell polarity loss of cell adhesion to other cells and extra cellular matrix ability to migrate and invade gained lowered E cadherin elevated N cadherin
what phenotype do cancer cells resemble after EMT
stem cell phenotype and morphology
how do transcription factors orchestrate EMT
wide range
different ones are activated in different cancers
all have similar actions despite their specific roles- overlapping results
EMT is orchestrated by the activation of specific transcription factors that are usually involved in embryogenesis
how do signalling pathways influences the EMT
growth factors and signalling pathways cross communicate with each other
e.g. activation of Ras also has a downstream effect of increased EMT transcription factors
what allows different mets to survive in different conditions
wide genetic variability mets due to heterogenic tumours
can mets themselves have subclones
yes
do the majority of solid tumours have a preferential metastatic site
yes
different for each cancer and each subtype of cancer
is it common for cancers to met to just one place
no
what are the theories for organ selectivity
mechanistic- blood flow
seed and soil- the provision of a fertile environment in which compatible cancer cells can grow (appropriate growth factors/ ECM environment, adhesion sites on endothelial lumenal surface- lock and key-, chemotaxis- soluble attraction factors from sites)
chemotaxis- formation of symbiotic relationship between 2nd site and tumour
why does the secondary site need to be fertile
as new tumours need time to establish and grow
what is the role of proteinases in invasion
lysis of matric proteins
degrades matrix
allows cancer cells to transclocate across ECM
what increases the expression of proteinases
cancer cells create signals that activate the expression of genes coding for these enzymes
what is the advantage of the rapid inactivation or activation of proteinases by cancer cells
can very quickly alter gene expression
allows them to turn on quickly- when they need to move/ migrate
turn off quickly when they need to recolonise
activated by cleavage and increased transcription
inactivated by inhibitors
what are the types of tumour cell invasion
collective (most common, connected by cell adhesions/ communication junctions, all undergo EMT at same time)
single cell
mesenchymal - fibroblast like invasion (e.g. melanoma, invades through collagen matrix, expressed e.g. intregins which allow pseudopodia formation and interact with stomral components)
what is anoikis
form of apoptosis that happen in the absence of a solid substrate - happens in blood vessels
what is dormancy
cancer cells lay dormant in vessels for extended period
