Cancer Metastasis

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Cancer Metastasis (Epithelial Cell Behavior Gone
Awry)
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I. Epithelial tissue architecture
Epithelial cells
Basement membrane
Connective tissue
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Focal adhesions
ACTIN
Integrin
ECM
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Cell junctions adherens junction
Cadherin
ACTIN
Cadherin
catenins
Farquhar Palade, 1963
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IV. Defining membrane domains
Epithelial cells are polarized
Apical (no adhesion)
Lateral (cadherin- based adhesion)
Basement membrane (extracellular matrix)
Basal (integrin-based adhesion)
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Discussion Topipc

• What steps would solid tumor cells need to
  undergo in order to colonize a metastatic tumor
  elsewhere in the body?

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Steps of Metastasis

• Detach cell-cell junctions from neighboring
  cells.
• Break through the basement membrane and invade
  locally.
• Enter the blood or lymphatic systems and survive.
• Adhere to a target tissue.

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Cell junctions adherens junction
Cadherin
ACTIN
Cadherin
catenins
How might this adhesion system be disassembled?
Farquhar Palade, 1963
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Dynamics of epithelial tissuesepithelial-mesench
yme transitions (EMT)
Specific epithelial cells receive signal
Cells protrude out of epithelium, disassemble
cell-cell junctions
Cells become mesenchymal (invasive and
migratory) and then differentiate to a new cell
type in another location.
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Breaking Cell-Cell Contacts
Slug, Snail
src
?
Cadherin
ACTIN
Cadherin
Cadherin
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Dynamics of epithelial tissuesepithelial-mesench
yme transitions (EMT)
Specific epithelial cells receive signal
Cells protrude out of epithelium, disassemble
cell-cell junctions
Cells become mesenchymal (invasive and
migratory) and then differentiate to a new cell
type in another location.
What might cells need to do to invade through the
basement membrane?
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Cell Migration
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• Cell protrudes the leading edge.
• New focal adhesions are assembled, anchoring the
  membrane to the ECM.
• Focal adhesions at the rear are disassembled.
• Traction forces from focal adhesions and stress
  fibers pull the cell forward.

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Dynamics of epithelial tissuesepithelial wound
healing
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HA/CD44 signaling
HA
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Metastatic Tumors
Colon cancer Breast cancer Testicular cancer
Liver cancer Lung cancer Brain cancer