13- Metastasis

Question 1

What is metastasis?

Answer 1

spreading to other tissues

Question 2

Which type of tumor (primary or secondary) that is responsible for the death of patients?

Answer 2

secondary

Question 3

What do cancer patients die of?

Answer 3

organ failure

Question 4

What (freeway) systems do tumor cells use to travel throughout the body?

Answer 4

lymphatic | circulatory

Question 5

What are metastatic cells called?

Answer 5

mets

Question 6

What is parenchyma?

Answer 6

tissue area of an organ that is functional (inner part)

Question 7

What is stroma?

Answer 7

tissue part of an organ that is structural (outer part)

Question 8

Which, stroma or parenchyma, do tumor cells originate from?

Answer 8

can be from both

Question 9

Is the method that tumor cells spread random or systematic (there is a pattern)?

Answer 9

there is a pattern

Question 10

What are nude mice?

Answer 10

mice with no immune system = allows us to study carcinogenesis

Question 11

What is intravasation? When does this happen?

Answer 11

tumor cells push through endothelial cells to get into the vessels | after angiogenesis

Question 12

What is extravasation?

Answer 12

tumor exits vessels &raquo_space;> replicates and grows secondary tumor on another organ

Question 13

What is Stage I of cancer?

Answer 13

local | no invasion

Question 14

What is Stage II of cancer?

Answer 14

some invasion | tumor cells not yet seen in lymph nodes (via biopsy)

Question 15

What is Stage III of cancer?

Answer 15

more invasion | begin to see tumor cells in lymph nodes = may need to resect lymph nodes

Question 16

What is Stage IV of cancer?

Answer 16

metastasized tumor cells = have invaded other tissues

Question 17

How do we know it’s metastasis versus a primary tumor?

Answer 17

primary tumor = a lot of disruption of tissue (due to invasion) | mets = more defined orders

Question 18

Why do tumor cells have a preference? Why do they go to certain areas?

Answer 18

tumors have cell-surface receptors &raquo_space;> when traveling throughout body = areas secreting chemicals that stimulate its receptors = will stay there

Question 19

What is “metastasis homing”?

Answer 19

dictated by the relative abundance of chemokines and receptors on the tumor cell = the more of both = will stay at that area

Question 20

What does “SCP” stand for?

Answer 20

single clonal population

Question 21

What does metastasis homing help explain in oncology?

Answer 21

explains the patterns of secondary tumor formation certain cancers associate with

Question 22

What are the 3 types of homing mechanisms?

Answer 22

selective growth | selective adhesion | selective chemotaxis

Question 23

What is the homing mechanism of selective growth?

Answer 23

selectively grow only in organs with appropriate growth environments, but travel aimlessly | no chemokines involved

Question 24

What is the homing mechanism of selective adhesion?

Answer 24

stick only to endothelial cells at site of organ that it calls home

Question 25

What is the homing mechanism of selective chemotaxis?

Answer 25

tumor cells only travel to where its chemokine is being secreted

Question 26

Where do these tumor cells get the receptor from that is involved with homing?

Answer 26

from the cells they used to be prior to de-differentiation

Question 27

Do tumor cells look for and go towards the circulatory system because they need more O2/nutrients or are they sensing chemokines?

Answer 27

they are sensing nutrients

Question 28

Where do tumor cells get the tools to cut through basal lamina?

Answer 28

tumor cells have access to every gene in the genome = turn on genes that can allow them to do this

Question 29

What does the ECM consist of?

Answer 29

fibronectin, collagen, many other proteins

Question 30

What are matrix degradation enzymes?

Answer 30

tools that the tumor cells use to get through ECM

Question 31

What are matrix metalloproteases?

Answer 31

matrix degradation enzyme | takes shape of chainsaw | can be secreted, mostly is a cell surface molecule

Question 32

What is the most dangerous thing about a tumor cell?

Answer 32

when it gains the ability to spread

Question 33

Why is surgery out as an option if the tumor has metastasized? What is the recommended treatment?

Answer 33

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

Question 34

What is TIMP2?

Answer 34

protein that inhibits metalloprotease from cutting their target = makes it harder for tumor cells to walk/invade

Question 35

Do all tumor cells need to have the ability to cut through the ECM?

Answer 35

no | tumor cells work as a team = some can break through ECM , others will follow | can also stimulate normal cells to produce metalloprotases

Question 36

Where do metalloproteases come from?

Answer 36

cells that need to replace connective tissue

Question 37

Why would connective tissue need to be replaced?

Answer 37

anti-aging | due to injuries

Question 38

What proteins are used to move through the ECM?

Answer 38

matrix metalloproteases | ADAM proteins | integrins | cadherins | CAMs | Selectins

Question 39

What are ADAM proteins?

Answer 39

disintegrin and metalloprotease | cuts certain adhesion molecules and other types of cell-surface molecules

Question 40

Which cells use the walking mechanism?

Answer 40

macrophages

Question 41

What are the 5 functions of cytoskeleton?

Answer 41

dynamic scaffolding providing structure | positioning organelles | provide tracks for movement of materials and organelles | cell movement | transduce signals

Question 42

How does a cell move towards a nutrient signal?

Answer 42

actin polymerization via actin filaments

Question 43

Explain the mechanism of actin polymerization and treadmilling.

Answer 43

whatever direction the actin is being added = direction cell is moving | actin is recycled | ARP allows for #D direction of polymerization

Question 44

What is the purpose of cell membrane protrusion and movement?

Answer 44

pushes cell membrane towards direction desired

Question 45

What does treadmilling allow the cell to do?

Answer 45

change shape and move

Question 46

What is Presenilin 1?

Answer 46

allows cell to know which direction it is going | in the focal points ("feet of cells") | involved in Alzheimer's

Question 47

What is the function of focal points in a cell?

Answer 47

allows cell to know where it is or what it is touching

Question 48

What are the hands that tumor cells use?

Answer 48

integrins

Question 49

What are integrins?

Answer 49

heterodimer | disulfide-alpha subunit = flexible "elbow" that can move and grab onto ECM proteins (connective fibers)

Question 50

How does a tumor cell know if integrin has grabbed onto something?

Answer 50

signal transduction pathway connected to integrin will tell the tumor cell

Question 51

Why would tumors need to change the kind of "hands" they are using?

Answer 51

depending on the environment they are in = helps with survival

Question 52

What do selectins bind to?

Answer 52

sugar molecules

Question 53

What are CAMs?

Answer 53

cell adhesion proteins

Question 54

What cells is basement membrane made out of?

Answer 54

endothelial cells

Question 55

How do selectins make tumor cells move? And on what?

Answer 55

tumor cells roll on the endothelial cells | tumor cells that are able to express glycoproteins which latch onto selectins

Question 56

What "hands" do the tumor cells use for extravasation?

Answer 56

CAMs -- cell adhesion molecules

Question 57

What is vinblastin?

Answer 57

interferes with cytoskeleton = can't put actin subunits together to make it work

Question 58

What affects does vinblastin have on tumor cell activity?

Answer 58

no treadmilling | inhibits actin polymerization | no cytokinesis

Question 59

What is taxol?

Answer 59

can't break actin-filament apart

Question 60

What affects does taxol have on tumor cell activity?

Answer 60

inhibits depolymerization of actin filaments