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Platelet-derived growth factor-mediated gliomagenesis and brain tumor recruitment
Elena I Fomchenko1, Eric C Holland
1Department of Cancer Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Abstract:
Platelet-derived growth factor (PDGF) is a growth factor family of ligands and receptors known to activate phosphatidylinositol 3-kinase, mitogen-activated protein kinase, Jak family kinase, Src family kinase, and phospholipase Cgamma signal transduction pathways, some of which have been causally linked to glioma formation. Extensive involvement of PDGF in development and its implication in a variety of pathologic conditions, including gliomagenesis, are mediated not only by autocrine effects but by paracrine effects. Many researchers view brain tumors as clonal entities derived from the cancer stem cell; however, recent documentation of the importance of the tumor microenvironment for glioma initiation and progression as well as the ability of neural stem or progenitor cells to migrate toward the sites of injury or tumor formation reveals additional complexities in brain tumorigenesis. Paracrine effects of PDGF in animal models of gliomagenesis, continued adult neurogenesis capable of increasing in response to brain injury, and the growth factor-rich environment of brain tumors suggest that recruitment may play a role in gliomagenesis. In this view, glioma formation involves recruitment of cells from the adjacent brain and possibly other sites.
Insights
Platelet-derived growth factor (PDGF) drives glioma formation through both internal cell signaling and external communication. PDGF may recruit cells to the tumor site, complicating brain tumor development.
Area of Science:
- Oncology
- Neuroscience
- Cell Biology
Background:
- Platelet-derived growth factor (PDGF) activates multiple signaling pathways implicated in glioma formation.
- PDGF's role in development and pathology extends to both autocrine and paracrine effects.
- Brain tumor initiation and progression are influenced by the tumor microenvironment and cell migration.
Purpose of the Study:
- To explore the complex role of PDGF in glioma initiation and progression.
- To investigate the contribution of paracrine PDGF signaling and cell recruitment in gliomagenesis.
- To integrate cancer stem cell models with the influence of the tumor microenvironment.
Main Methods:
- Review of signaling pathways activated by PDGF, including PI3K, MAPK, JAK, Src, and PLCγ.
- Analysis of PDGF's involvement in both normal development and pathological conditions like gliomagenesis.
- Consideration of cell migration, neurogenesis, and the tumor microenvironment in brain tumorigenesis.
Main Results:
- PDGF signaling pathways are causally linked to glioma formation.
- Paracrine PDGF effects, alongside adult neurogenesis and the tumor microenvironment, suggest cell recruitment in gliomagenesis.
- Glioma formation may involve the recruitment of cells from adjacent brain areas.
Conclusions:
- PDGF plays a multifaceted role in glioma development, involving both intracellular signaling and extracellular recruitment mechanisms.
- The tumor microenvironment and cell migration, influenced by paracrine PDGF, are critical factors in brain tumorigenesis.
- Understanding PDGF's paracrine functions is essential for comprehending glioma initiation and progression.
