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

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

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

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

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

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

Cancer

• Uncontrolled growth (proliferation)• Invasion into surrounding tissues• Metastasis (spread to other areas in body)

Key terms:Malignant

Proto-oncogeneOncogene

Tumor suppressor gene

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?