13- Metastasis Flashcards
What is metastasis?
spreading to other tissues
Which type of tumor (primary or secondary) that is responsible for the death of patients?
secondary
What do cancer patients die of?
organ failure
What (freeway) systems do tumor cells use to travel throughout the body?
lymphatic | circulatory
What are metastatic cells called?
mets
What is parenchyma?
tissue area of an organ that is functional (inner part)
What is stroma?
tissue part of an organ that is structural (outer part)
Which, stroma or parenchyma, do tumor cells originate from?
can be from both
Is the method that tumor cells spread random or systematic (there is a pattern)?
there is a pattern
What are nude mice?
mice with no immune system = allows us to study carcinogenesis
What is intravasation? When does this happen?
tumor cells push through endothelial cells to get into the vessels | after angiogenesis
What is extravasation?
tumor exits vessels »_space;> replicates and grows secondary tumor on another organ
What is Stage I of cancer?
local | no invasion
What is Stage II of cancer?
some invasion | tumor cells not yet seen in lymph nodes (via biopsy)
What is Stage III of cancer?
more invasion | begin to see tumor cells in lymph nodes = may need to resect lymph nodes
What is Stage IV of cancer?
metastasized tumor cells = have invaded other tissues
How do we know it’s metastasis versus a primary tumor?
primary tumor = a lot of disruption of tissue (due to invasion) | mets = more defined orders
Why do tumor cells have a preference? Why do they go to certain areas?
tumors have cell-surface receptors »_space;> when traveling throughout body = areas secreting chemicals that stimulate its receptors = will stay there
What is “metastasis homing”?
dictated by the relative abundance of chemokines and receptors on the tumor cell = the more of both = will stay at that area
What does “SCP” stand for?
single clonal population
What does metastasis homing help explain in oncology?
explains the patterns of secondary tumor formation certain cancers associate with
What are the 3 types of homing mechanisms?
selective growth | selective adhesion | selective chemotaxis
What is the homing mechanism of selective growth?
selectively grow only in organs with appropriate growth environments, but travel aimlessly | no chemokines involved
What is the homing mechanism of selective adhesion?
stick only to endothelial cells at site of organ that it calls home
What is the homing mechanism of selective chemotaxis?
tumor cells only travel to where its chemokine is being secreted
Where do these tumor cells get the receptor from that is involved with homing?
from the cells they used to be prior to de-differentiation
Do tumor cells look for and go towards the circulatory system because they need more O2/nutrients or are they sensing chemokines?
they are sensing nutrients
Where do tumor cells get the tools to cut through basal lamina?
tumor cells have access to every gene in the genome = turn on genes that can allow them to do this
What does the ECM consist of?
fibronectin, collagen, many other proteins
What are matrix degradation enzymes?
tools that the tumor cells use to get through ECM
What are matrix metalloproteases?
matrix degradation enzyme | takes shape of chainsaw | can be secreted, mostly is a cell surface molecule
What is the most dangerous thing about a tumor cell?
when it gains the ability to spread
Why is surgery out as an option if the tumor has metastasized? What is the recommended treatment?
because tumor has spread = surgery will be more risky as opposed to taking out one tumor, now it is many tumors | depend on chemotherapeutic drug targeting metalloproteases
What is TIMP2?
protein that inhibits metalloprotease from cutting their target = makes it harder for tumor cells to walk/invade
Do all tumor cells need to have the ability to cut through the ECM?
no | tumor cells work as a team = some can break through ECM , others will follow | can also stimulate normal cells to produce metalloprotases
Where do metalloproteases come from?
cells that need to replace connective tissue
Why would connective tissue need to be replaced?
anti-aging | due to injuries
What proteins are used to move through the ECM?
matrix metalloproteases | ADAM proteins | integrins | cadherins | CAMs | Selectins
What are ADAM proteins?
disintegrin and metalloprotease | cuts certain adhesion molecules and other types of cell-surface molecules
Which cells use the walking mechanism?
macrophages
What are the 5 functions of cytoskeleton?
dynamic scaffolding providing structure | positioning organelles | provide tracks for movement of materials and organelles | cell movement | transduce signals
How does a cell move towards a nutrient signal?
actin polymerization via actin filaments
Explain the mechanism of actin polymerization and treadmilling.
whatever direction the actin is being added = direction cell is moving | actin is recycled | ARP allows for #D direction of polymerization
What is the purpose of cell membrane protrusion and movement?
pushes cell membrane towards direction desired
What does treadmilling allow the cell to do?
change shape and move
What is Presenilin 1?
allows cell to know which direction it is going | in the focal points (“feet of cells”) | involved in Alzheimer’s
What is the function of focal points in a cell?
allows cell to know where it is or what it is touching
What are the hands that tumor cells use?
integrins
What are integrins?
heterodimer | disulfide-alpha subunit = flexible “elbow” that can move and grab onto ECM proteins (connective fibers)
How does a tumor cell know if integrin has grabbed onto something?
signal transduction pathway connected to integrin will tell the tumor cell
Why would tumors need to change the kind of “hands” they are using?
depending on the environment they are in = helps with survival
What do selectins bind to?
sugar molecules
What are CAMs?
cell adhesion proteins
What cells is basement membrane made out of?
endothelial cells
How do selectins make tumor cells move? And on what?
tumor cells roll on the endothelial cells | tumor cells that are able to express glycoproteins which latch onto selectins
What “hands” do the tumor cells use for extravasation?
CAMs – cell adhesion molecules
What is vinblastin?
interferes with cytoskeleton = can’t put actin subunits together to make it work
What affects does vinblastin have on tumor cell activity?
no treadmilling | inhibits actin polymerization | no cytokinesis
What is taxol?
can’t break actin-filament apart
What affects does taxol have on tumor cell activity?
inhibits depolymerization of actin filaments
