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Cancer Biology > Chapter 9 > Flashcards

Chapter 9 Flashcards

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1
Q

What does the tumor microenvironment consist of?

A

It consists of normal cells, immune cells, TAM (tumor associated macrophages), fibroblasts

The environment in which the tumor resides that supports it.

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2
Q

True or false: Most of the cell within our body reside within a particular tissue or organ.

A

True

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3
Q

What is the basement membrane?

A

It is an acellular (without cells) support for epithelial, endothelial, and some mesenchymal cells

  • It acts as a barrier to separate tissue compartments.
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4
Q

What extracellular matrix proteins might be present within the basement membrane?

A
  1. Laminins
  2. Collagens
  3. Proteoglycans
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5
Q

Real quick: what are the three differences between benign and malignant?

A

Benign
1. encapsulated
2. resembles parent tissue
3. grows slow

Malignant
1. non-encapsulated
2. unlike parent tissue
3. grows fast

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6
Q

True or false: the basement membrane lies between the endothelial lining of capillaries and the epithelial cells.

A

True

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7
Q

What truly distinguishes a malignant tumor from a benign one?

A

metastasis

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8
Q

True or false: most solid tumors have NOT metastasized by the time of diagnosis.

A

False

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9
Q

What are the three ways that metastasis cause issues?

A
  1. It physically gets in the way
  2. It competes for nutrients and oxygen with other cells present
  3. It interferes with normal organ function
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10
Q

True or false: metastasis is random

A

False

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11
Q

What does the term organotropism mean?

A

It means that specific cancers metastasize to specific sites

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12
Q

What explains 2/3 of the reasons for why a cancer goes to a specific location?

A

The directionality of blood flow

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13
Q

What is an example of how the directionality of blood flow impacts where a cancer goes?

A

Ewing guy found out that colon cancer likes to go to the liver.

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14
Q

What is the seed and soil theory?

A

It is the theory that not only the seed (the cancer cells) but also the environment that they are going to play a role in where they go

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15
Q

What is the support for the seed and soil theory?

A
  1. There are receptors that line the capillaries in organs where the cancer spreads that allow for metastasis to that site.
  2. Pre-metastatic niche
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16
Q

What is the pre-metastatic niche refer to?

A

It refers to the cancers ability to send signals that alter the site of future metastasis to prepare for the tumor cells’ arrival.

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17
Q

Primary tumors are a heterogeneous mix of subclones.

What does this mean?

A

This means: within a single tumor, there are multiple, separate populations of cancer cells (subclones) that have different genetic mutations and characteristics. They can behave differently, including varying in their ability to grow, invade tissues, or resist treatment.

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18
Q

Explain what a monoclonal and branched spread would entail.

A

A spread characterized as monoclonal and branched would have the primary tumor having two different metastases that each contained only one type of sub colony.

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19
Q

Explain what a polyclonal and linear spread would entail.

A

This would be if a primary tumor had one metastases that contained more than one type of sub colony.

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20
Q

Explain what a polyclonal and branched spread would look like.

A

This would be if a primary tumor had two metastases that each had more than one type of sub colony.

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21
Q

What is cross-seeding?

A

It refers to what happens when a subclone of a metastases further metastasizes.

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22
Q

Generally, what are the steps of metastasis? (6)

A
  1. Invasion
  2. Intravasation
  3. Transportation
  4. Extravasation
  5. Metastatic colonization
  6. Angiogenesis
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23
Q

What affects a tumors’ ability to spread?

A
  1. The tumor microenvironment
  2. Subpopulation of CSCs
  3. Production of signalling molecules
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24
Q

What does EMT stand for?

What is it?

A

It stand for epithelial mesenchymal transition

EMT when cells leave an epithelial layer and become a loose mass of mesenchymal cells that can migrate individually.

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25
Q

What is EMT important for?

A

It is important for gastrulation and early development

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26
Q

What is EMT characterized by?

A
  1. Loss in cell polarity - loss of order
  2. Deconstruction of epithelial cell-cell junctions
  3. Changes in cell shape
  4. Downregulation of the epithelial markers (E cadherin)
  5. Upregulation of mesenchymal proteins (N cadherin)
  6. Secretion of proteases (matrix metalloproteases)
  7. Increased motility
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27
Q

Generally speaking, how is EMT induced?

A

by factors that are secreted by the tumor stroma

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28
Q

What do these factors do?

A

They bind to tumor cells near and result in intracellular signalling - signal transduction pathways.

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29
Q

What is the result of the signal transduction pathways caused by the factors within the tumor stroma?

A

The result is the activation of transcription factors that cause the transcription of genes that are needed for EMT.

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30
Q

True or false: as cells undergo EMT, the begin to express stem cell markers.

A

True

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31
Q

What are some molecules that are important for invasion?

A
  1. Cell-adhesion molecules
  2. Integrins
  3. Proteases
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32
Q

What do CAMs (cell adhesion molecules) do?

A

They mediate homotypic and heterotypic cell recognition.

aka they help identify and adhere to cells that are either the same or different from each other

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33
Q

What are cadherins?

A

They are a type of CAM that are calcium dependent transmembrane glycoprotein that interact with the cytoskeleton via catenins.

34
Q

Why is E cadherin considered a tumor suppressor?

A

Because it tells other cells around it that it still wants to be an epithelial cell.

35
Q

What are catenins?

A

Catenins are molecules that exist within the cell and bind to transcription factors that induce gene expression.

Think of Beta catenin from chapter 8.

36
Q

is N cadherin considered a tumor suppressor or a proto-oncogene?

A

It is considered a proto-oncogene.

37
Q

Generally, what is the ECM?

A

It is the heterogeneous mix of materials that surround cells.

38
Q

Cell membranes adhere to the ECM.

How do they do this?

A

They do this by action of integrin.

39
Q

What is integrin?

A

It is a transmembrane protein that binds to the ECM outside of epithelial cells and to the actin filaments within those cells.

40
Q

Is the binding of integrin covalent or noncovalent?

A

It is noncovalent and depending on how weak it is, it can move more or less.

41
Q

How does a cell move within the tissue?

A

It moves within the tissue by binding and and reattaching the integrin to the matix.

42
Q

How is the movement of a cell important?

A

It is important during embryonic development as well as when cancer cells spread (trying to get to the capillary).

43
Q

True or false: integrins mediate cell ECM interactions and intracellular signal transduction.

A

True.

44
Q

Integrins are a family of 24 heterodimers that are made up of a alpha and beta subunit.

What does this mean?

A
45
Q

What determines the type of interaction the integrin will have with the ECM?

A

The combination of subunits.

aka: different combinations can interact with different stuff.

46
Q

Explain the three importances of integrins.

A
  1. They cluster in the membrane once bound to a ligand and affect the cytoskeletal arrangement.
  2. They display inside-out signalling (EGF is outside in) *this is the reverse - intracellular signals modify integrins.
  3. They play a role in anoikis - homelessness cell death (aka when integrins don’t have a suitable ECM ligands they will recruit caspase 8
47
Q

How might integrins be altered in cancer cells?

A

They would probably be overexpressed and would be unable to recruit apoptotic factors like the previously mentioned capase 8

48
Q

Why are proteases important for invasion?

A

They degrade a path through the ECM

  • they upregulate MMPs
49
Q

What are MMPs

What do they do?

A

MMPs are matrix matalloproteases

They act to cleave the extracellular domain of E cadherin

50
Q

What do tumor cells do in relation to MMPs?

A

They upregulate them

51
Q

What is the degree of upregulation associated with?

A

It is associated with the progression of the cancer.

52
Q

What can tumor cells do to surrounding stromal cells in relation to MMPs?

A

They can induce them to produce MMPs

53
Q

The second step to metastasis is intravasation. What is this?

A

It is the entry of tumor cells in a blood or lymph vessel

54
Q

What MUST tumor cells do to get into the said vessel?

A
  1. Attach to stromal face of the vessel
  2. Degrade the basement membrane of the blood vessel
  3. Pass through the endothelial cells
55
Q

What type of cells assist tumor cells in intravasation?

A

Tumor associated macrophages

56
Q

What are the new vessels formed by the tumor characteristically like?

A

They are leakey and tortuous.

Leaky allows more tumor cells to get in

Tortuous means twisty

57
Q

Intravasation occurs at the assembly of three cell types.

What are they?

A
  1. Perivascular macrophage
  2. Tumor cell that is overexpressing MENA which is mammalian enabled actin binding protein
  3. The endothelial cell
58
Q

What does TMEM doorways stand for?

What are they?

A

It stands for Tumor microenvironment of metastasis doorways

This is the assemblage of three cell types (listed in the previous question) that act passages to the circulation.

59
Q

What are circulating tumor cells?

A

They are tumors that are within the bloodstream.

60
Q

What are the characteristics of circulating tumor cells?

A
  1. They travel in one direction
  2. They can be transported by themselves or as emboli (clots)
61
Q

What advantages does traveling as clots give to tumor cells?

A
  1. They can hide from the immune system
  2. It protects them from the force of blood
62
Q

True or false: many cancers metastasize to the first pass organ.

A

True.

63
Q

Why are circulating tumor cells being studied heavily today?

A

Circulating tumor cells (CTCs) are being heavily studied for early cancer detection, monitoring disease progression, understanding metastasis, and enabling personalized treatment through liquid biopsy.

64
Q

After transport, what is the next step in metastasis?

What is the site of metastasis influenced by?

A

Extravasation

The location of the extravasation as well as the surrounding Tumor Microenvironment of the stroma

65
Q

What happens to many tumor cells in relation to extravasation?

Why is this?

How do they do this?

A

They get trapped in the first capillary beds that they encounter.

Because tumor cells are 20-30 micrometers, whereas the diameter of the capillaries are 8 micrometers

They link to the endothelial cells through ligands and receptors

66
Q

What is paracellular transendothelial migration?

Is there evidence for this?

A

Moving in between endothelial cells through endothelial cell junctions.

Yes this is the main way extravasation occurs.

67
Q

What about transcellular transendothelial migration?

Is there evidence for this?

A

This is moving directly through cells and requires an active transport of some sort - not really well understood.

There is limited evidence for this.

68
Q

What are the basic steps to extravasation?

A
  1. Tumor cell attach to the endothelial side of blood vessel
  2. They either pass through or between endothelial cells and the basement membrane
  3. Finally migrate into the surrounding stroma
69
Q

What does the evidence supporting the roles of proteases in the step of extravasation say?

A

It is really inconclusive at the moment.

70
Q

Regarding metastatic colonization, what must tumors do to form a good colony in the new tissue?

A

They must adapt the specific organ.

71
Q

What are DTCs?

A

These are disseminated tumor cells - or cells that have spread to a distant site, but have not yet colonized.

72
Q

What is a micrometastasis?

A

It is collection of DTCs that may remain dormant for years and don’t really show progressive growth, entering a state of quiescence.

73
Q

What is metastatic colonization?

A

It is the establishment of a progressively growing tumor at a distant site.

74
Q

What does metastatic colonization involve?

A
  1. the formation of new blood vessels
  2. many of the cells show epithelial morphology, meaning they underwent some sort of transition.
75
Q

Establishment of a pre-metastatic niche may be important for successful colonization.

What study showed this?

A

Mouse study showed that bone marrow derived cells arrived at the sites of metastasis before the tumor cells themselves.

76
Q

What are exosomes?

A

They are small vesicles that carry proteins and nucleic acids.

77
Q

Exosomes display horizontal transfer to cells in which they fuse.

What does this mean?

A

It means move from cell to cell without replication.

78
Q

What are exosomes important for?

A
  1. They are important for communication between cells.
  2. There is also evidence that tumor secreted exosomes can help establish the pre-metastatic niche.
79
Q

What are metastasis suppressor genes?

What might they do?

A

They are genes that inhibit overt metastasis without affecting growth of the primary tumor.

They can affect MAPK signalling and gap junction communication.

80
Q

How can miRNAs also prevent metastasis?

A

They control the degradation of mRNA.

Cancer Biology (11 decks)

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