The Microenvironment, Stem Cells, and Cancer

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The Microenvironment, Stem Cells, and Cancer
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Microenvironment

• Signaling molecules
• G-CSF
• Erythropoietin
• Cell-cell contact
• Adherens junctions
• Gap Junctions
• Desmosomes

• Extracellular matrix
• Collagen
• Fibronectin
• Laminin
• Forces
• Elasticity
• Compression
• Stiffness

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Niche Stem cell behavior control

• Adult stem cells such as intestinal crypt stem
  cells are tightly regulated by the environment
  around them
• View Intestinal Crypt Stem Cells - A Clonal
  Conveyor Belt
• Sometimes mutations cause bad behaviors
• Stem cells have the property to divide
  asymmetrically
• One daughter cell stays a stem cell
• The other daughter cell changes, or differentiates

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Blood cell differentiation

• Granulocyte Colony Stimulating Factor
• Erythropoietin
• Push common myeloid progenitor cell to become red
  blood cells or white blood cells (leukocytes)
• G-CSF and Epo are signaling molecules that
  initiate signaling pathways that lead to gene
  expression and phenotype change
• Transcription and translation

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Cell interactions

• Tight junctions
• Form a fluid and ion impermeable sheet
• Allows for different functions on different sides
  of the sheet
• Anchoring junctions
• Two types adherens and desmosomes
• Built from cadherins (outside) and catenins
  (inside)
• Adherens attach to actin cytoskeleton
• Desmosome (strong) attach to keratin filaments
• Gap junctions
• Channels between cells

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The Matrix

• Like a stem cells dorm room
• Concrete, rebar, wood posts, furniture
• Cells reside within this non-living world
• In the body the extracellular matrix gives
  tissues their structural and mechanical
  properties
• The components of the matrix contribute to tissue
  specificity of cells

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Forces

• Elasticity what is the stiffness of a tissue?
• Brain lt skin lt muscle lt bone
• Cells can sense the tissue stiffness
• They can also respond to the stiffness by
  changing shape and gene expression
• Mesenchymal stem cells grown on gels
• Stiffnessbrain neurons
• Stiffnessmuscle myoblasts
• Stiffnessbone osteoblasts

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Cancer

• Uncontrolled growth (proliferation)
• Invasion into surrounding tissues
• Metastasis (spread to other areas in body)
• Key terms
• Malignant
• Proto-oncogene
• Oncogene
• Tumor suppressor gene

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Thought questions

• Is DNA mutation necessary for cancer?
• Could cancer occur only by manipulating the
  microenvironment?
• If you took a piece of normal tissue and inserted
  it inside a tumor, what would happen?
• If you infect a chicken embryo with a
  cancer-causing virus, and the chicken grew up
  cancer-free, would you assume the chickens cells
  were cured of cancer?
• How might we test ways to see if certain
  microenvironments can stop cancer from growing?