Many growth factor pathways are ____? This leads to a concern of what?
- proto-oncogenes
2. Gain of function mutations –> oncogenes
Epidermal Growth Factor (EGF)
- found in: activated macrophages, salivary glands, keratinocytes, and many more
- function: mitogenic for keratinocytes and fibroblasts; stimulate keratinocyte migration; stimulates formation of granulation tissue
Transforming Growth Factor alpha (TGF-alpha)
- found in: activated macrophages, keratinocytes, and many more
- function: stimulate proliferation of hepatocytes and many other epithelial cells
What is important about the ERBB2 receptor?
- aka HER2
- over expressed in breast cancer
How are EGF and TGF-alpha related?
same family (EGF)
Platelet Derived Growth Factor (PDGF)
- found in: platelets, macrophages, endothelial cells, SM cells, keratinocytes
- function: chemotactic for neutrophils, macrophages, fibroblasts, and SM cells; activates/stimulates proliferation of fibroblasts, endothelial, and other cells; stimulates ECM protein synthesis
Hepatocyte Growth Factor (HGF)
- found in: fibroblasts, stromal cells in liver, endothelial cells
- function: enhances proliferation/survival of hepatocytes and other epithelial cells; increases cell motility/migration
- acts as morphogen in embryonic development
- receptor is MET
- frequently over expressed or mutate din tumors
What GF is often mutated in renal or thyroid papillary cancers?
HGF
*MET inhibitors can be a good tx
Vascular Endothelial Growth Factor (VEGF)
- found in: Mesechymal cells
- function: stimulates proliferation of endothelial cells; increases vascular permeability
*most types just have letter after name, but PIGF (placental GF) is a VEGF
- VEGF-A: angiogenic
- VEGF-B/PIGF: embryonic vessel development
- VEGF C/D: angiogenic + lymphatic development
Fibroblast Growth Factors (FGFs) (FGF 1 + FGF 2)
- found in: macrophages, mast cells, endothelial cells, many other types
- function: chemotactic and mitogenic for fibroblasts; stimulate angiogenesis and ECM protein synthesis; respond to wound healing
Transforming Growth Factor Beta (TGF-beta)
- found in: platelet, T cells, macrophages, endothelial cells, keratinocytes, SM cells, fibroblasts
- function: chemotactic for leukocytes and fibroblasts; stimulates ECM protein synthesis; suppresses acute inflammation
Keratinocyte Growth Factor (KGF)
- found in: fibroblasts
- function: stimulates keratinocyte migration, proliferation, and differentiation
What is the most important producer of VEGFs?
hypoxia
What GF is the most important for angiogenesis?
VEGFR-2
FGF-7 is also referred to as?
KGF
Which GF drives scar formation? what else does it do?
- TGF-beta - it stimulates production of collagen, fibronectin, and proteoglycans; and it inhibits collagen degradation by decreasing MMPs and increasing TIMPs
- stops inflammation; drive fibrosis in lung, liver, and kidney in setting of chronic inflammation
What synthesizes interstitial matrix?
Mesenchymal cells like fibroblasts
What are the three groups of proteins that comprise the ECM? Their function?
- Fibrous structural: collagen, elastin; confer tensile strength and recoil
- Water-hydrated gels: proteoglycans and hyaluronan; permit compressive resistance and lubrication
- Adhesive glycoprotein: connect ECM to other ECM/cells
Collagen synthesis depends on what?
vitamin C
