TME and cell communication

• Describe the actions of fibroblasts in the TME

  • Secrete growth factors, cytokines and ECM components that alter the properties of the microenvironment and promote tumour growth
  • Create a physical barrier around the tumour, which blocks immune cell and drug entry
  • Communicate with cancer cells to promote tumour survival
  • Cancer and stromal cells secrete TGF-beta, PDGF and fibroblast growth factor in order to convert fibroblasts into cancer associated fibroblasts (CAFs)
• Describe the relationship between myofibroblast density and patient survival

  Myofibroblast predicts clinical progression of cancer and therefore patient survival time. Higher densities of cancer associated fibroblasts relate to much poorer prognosis.
• Describe the role of the ECM in TME

  • Sequester growth factors, which can be liberated later during ECM digestion, which generates local high concentrations and triggers growth signalling to cancer cells.
  • ECM can promoter tumour growth and progression
  • Create a physical barrier around the tumour, which blocks immune cell entry
  • Glycan modification can alter the structural properties of the matrix, which is implicated in cancer progression
• Describe the importance of the stroma in the TME

  • The composition and functional state of tumour microenvironment affects cancer progression and treatment
  • For cancer to advance, it must manipulate cells in the TME, in order to metastasise.
  • Components of the tumour microenvironment vary by tissue type and patient and coevolve with the tumour as it progresses.
• What is heterotypic signalling?

  This is communication between dissimilar cell types, such as cancer cells and stromal cells. Example:

  • Fibroblast Growth factor 10 ligand is secreted by stromal cells and binds to FGF receptors in cancer cells.

  Stromal cells can secrete mitogenic growth factors, growth inhibitory signals and trophic factors.
• Describe the different types of heterotypic cell communication

  Autocrine: cell stimulates itself

  Paracrine: cell stimulates adjacent cell

  Juxtacrine: cell stimulates connected cell