5
Onko (Subject) / x20 Sampson (Lesson)
- List three different cell types found in stromal tissue Nerves, blood vessels, immune cells, fibroblasts, smooth muscle cells
- Name three common molecular markers whose up-regulation is used to identify carcinoma-associated fibroblasts fibroblast activation protein (FAP), alpha smooth actin (SMA), fibroblast specific protein (FSP1), CD90/Thy1, platelet derived growth factor receptors, Tenascin C, podoplanin
- Describe three mechanisms by which carcinoma-associated fibroblasts exert tumor-promoting effects secrete paracrine-acting soluble factors; direct cell-cell contacts with tumor cells, ECM remodeling; angiogenesis; modulate immune response; metabolic reprogramming
- Name three molecular factors that play critical roles in remodeling the extracellular matrix in the tumor-associated stroma Rho-ROCK, Caveolin-1 (Cav-1), Yes-associated protein (YAP) & transcriptional co-activator with PDZ-binding motif
- Name three mechanisms by which the tumor-associated extracellular matrix can exert immune-suppressive effects ECM can inhibit T-cell proliferation via type I collagen ligation of LAIR receptors and T-cell activation from a naïve state T cell activity prevented by ECM via impaired antigen presentation by APCs (stiffened ECM compromised T cell activation by CD3 and CD28 possibly by impairing IL-2 production, which is required for T-cell proliferation and Th1-cell differentiation) Regions of densely packed ECM shows lymphocyte displacement Collagen-rich/rigid ECM promotes macrophage proliferation /activation and favors the pro-tumorigenic M2 polarization phenotype Macrophage infiltration requires expression of collagen receptor DDR1 but inhibited by ECM protein SPARC
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