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The Microenvironment, Stem Cells, and Cancer

The Microenvironment, Stem Cells, and Cancer. 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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The Microenvironment, Stem Cells, and Cancer

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  1. The Microenvironment, Stem Cells, and Cancer

  2. Microenvironment • Signaling molecules • G-CSF • Erythropoietin • Cell-cell contact • Adherens junctions • Gap Junctions • Desmosomes • Extracellular matrix • Collagen • Fibronectin • Laminin • Forces • Elasticity • Compression • Stiffness

  3. 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

  4. 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

  5. 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

  6. The Matrix • Like a stem cell’s 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

  7. Forces • Elasticity: what is the stiffness of a tissue? • Brain < skin < muscle < 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

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

  9. 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 chicken’s cells were cured of cancer? • How might we test ways to see if certain microenvironments can stop cancer from growing?

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