Todays topics

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Todays topics

• Tumor microenvironment
• extracellular matrix
• fibroblasts
• immune cells

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Cancer Cells exist in a complex environment
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Tissue MicroenvironmentBhowmick et al, Nature
2004

• ECM
• Basement membrane secreted by epithelium
• Helps confer tissue specificity, polarity and
  function
• Stroma secreted by fibroblasts
• Growth factors
• Non-epithelial cell types
• Vasculature
• Next week
• Immune cells
• Secrete growth factors (stimulate proliferation)
• Generate reactive oxygen species (DNA damage)
• Fibroblasts
• Synthesis, deposition and remodelling of much of
  the tumor ECM

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Stroma associated with tumors is vastly different
than stroma associated with normal tissues
Bhowmick et al., Nature, 2004

• Growth factor production by the cancer can
  influence cells in the microenvironment

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• Interactions between the epithelium and stroma is
  a careful balancing act. Loss of regulation in
  one can influence the other.
• EGF/TGFß signals counterbalance each other. Loss
  of one or overexpression of the other can
  initiate proliferation.

Bhowmick et al., Nature, 2004
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Tumors and inflammation

• Tumors can be sites of inflammation
• Due to changes in blood supply, there is
  frequently necrosis, hypoxia
• Tumors can attract immune cells
• Some immune cells promote tumor growth
• TAM tumor associated macrophage

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Ben-Baruch, Breast cancer research, 2002
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Yu and Rak, Breast Cancer Research, 2003
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Tissue MicroenvironmentBhowmick et al, Nature
2004

• ECM
• Basement membrane secreted by epithelium
• Helps confer tissue specificity, polarity and
  function
• Stroma secreted by fibroblasts
• Growth factors
• Non-epithelial cell types
• Vasculature
• Next week
• Immune cells
• Secrete growth factors (stimulate proliferation)
• Generate reactive oxygen species (DNA damage)
• Fibroblasts
• Synthesis, deposition and remodelling of much of
  the tumor ECM

10
Cancer Cells exist in a complex environment