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Disease and Defense: Unit 2 > Neoplasia: Invasion & Metastasis > Flashcards

Neoplasia: Invasion & Metastasis Flashcards

1
Q

Define: Metastasis.

A

The transfer of malignant cells from the primary site to a non-connected (secondary) site

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2
Q

Dissemination of cancers may occur in through three pathways. What are they?

A
  1. Cavitary- Direct seeding of body cavities or surfaces
  2. Lymphatogenous- lymphatic spread
  3. Hematogenous spread- Spread through blood
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3
Q

What motivates cancer cells in a primary tumor to metastasize?

A

It is advantageous to move away from the primary tumor when conditions get crowded and harsh (hypoxia and lack of nutrition)

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4
Q

What protein keeps epithelial cells bound to each other?

A

E-Cadherin.

  • Cadherin family thransmembrane glycoproteins
  • Bound to B–catenin and actin cytoskeleton
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5
Q

What are four mechanisms by which E-Cadherin expression is lost.

A
  1. Loss of heterzygosity
  2. Inactivating mutation (rare)
  3. Silencing of gene expression via hypermethylation of promotor by transcriptional repressors
  4. Transcription factors promote epithelial-to-mesenchymal transitions
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6
Q

How does the cell promote epithelial-to-mesenchymal transition?

A

Repressing transcription of the E-cadherin gene

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7
Q

What enzyme does the tumor cell utilize to degrade local basement membranes?

A

Matrix metalloproteinases

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8
Q

MMPs cleave collagens and proteoglycans. These cleavage products have three properties. What are they?

A
  1. Chemotactic
  2. Angiogenic
  3. Growth-promoting effects
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9
Q

What are the two modes of movement of cancer cells through the basement membrane?

A
  1. Degradation of basement membrane with MMPs

2 Ameboid migration between the spaces in the matrix

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10
Q

What is the third step of invasion of a cancer cell?

A

Changes in attachment of tumor cells to the ECM protein.

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11
Q

Cancer cells can move through the ECM by producing tumor-derived cytokines that aide in their own movement. Give an example of one of these cytokines.

A

Autocrine motility factor

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12
Q

Name two components of the ECM that when cleaved are chemotactic for tumor cells.

Name two growth factors of the ECM that are chemotactic for the tumor cells.

A
  1. Collagen and Laminin

2. IGFs I and II (Insulin-like Growth Factor)

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13
Q

What do stromal cells produce that has an effect on tumor cell migration?

A

Paracrine

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14
Q

What is intravasation?

A

The invasion of cancerr cells through the basal membrane into the blood

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15
Q

How do cancer cells survive in circulation?

A

They aggregate into clumps. They can do this either by:

  1. Adherence to other cancer cells
  2. Binding to platelets
  3. Binding to coagulation factors&raquo_space;» formation of emboli
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16
Q

Explain the steps of extravasation.

A
  1. Adhesion to the endothelium
  2. Egress through basement membrane (CD44 expressed on T cells and cancer cells)
  3. Many cancer cells leave at the first capillary bed encountered
17
Q

How does CD44 help cancer cells metastasize?

A

CD44 is used in cancer cells to migrate to selective sites in the lymphoid tissues

18
Q

What is the “Seed and Soil” Theory?

A

Theory that explains why cancer cells may target certain organs.

  1. Extravasation- Endothelial cells of different organs have different ligands that cells target
  2. Tumor cells have chemokine receptors that arre attracted to chemokines secreted by different tissues
  3. Some tissues are nonpermissive
19
Q

What is dormancy?

A

Prolonged survival of micrometastases without progression,

20
Q

What do cancer cells release to effect stromal cells?

What effect does that have on stromal cells?

A

Cytokines
Growth Factors
ECM molecules

Stromal cells make the metastatic site more habitable

21
Q

Name four theories that have been proposed to explain how the metatstatic phenotype arises?

A
  1. Many cells, many mutations (Darwinism)
  2. Mutation is there early and in most cells
  3. Individual gene variation results in cancers metastisizing.
  4. Microenvironment
22
Q

Name two ultimate effects of metastases.

A
  1. Direct- Invasive masses which interfere with normal funciton
  2. Indirect: Paraneoplastic syndrome
23
Q

Name some characteristics of paraneoplastic syndrome.

A
  • Ectopic Hormone Production- Hormones produced by tumors
  • Cutaneous Lesions
  • Arthropathies- disease of the joint
  • Myopathies- disease of the muscle
  • Neuropathies- disease of the nervous system
  • Multiple thromboses
  • Nephrosis- kidney disease
  • Cachexia- Weakness and wasting of the body due to severe chronic illness
24
Q

What are the ultimate causes of death from cancer?

A 
Infection 48%
Organ Failure 19.2%
Thromboembolism 12.2%
Hemorrhage 8.8%
Emaciation 7.7%

Disease and Defense: Unit 2 (12 decks)

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