Definition
- PDGFR is a receptor tyrosine kinase involved in cell growth, differentiation, and angiogenesis.
- It is mainly expressed on mesenchymal cells (fibroblasts, smooth muscle cells, pericytes).
Structure and Types
- Two main types:
- PDGFR-α (alpha)
- PDGFR-β (beta)
- These can form homodimers (αα or ββ) or heterodimers (αβ) upon ligand binding.
- Each receptor has:
- An extracellular ligand-binding domain
- A transmembrane domain
- An intracellular tyrosine kinase domain
Activation by PDGF Ligands
- Activated by platelet-derived growth factor (PDGF) ligands (PDGF-AA, BB, AB, etc.)
- Ligand binding → receptor dimerization → autophosphorylation
- Triggers intracellular signaling (e.g., PI3K/AKT, RAS/MAPK pathways)
- Leads to:
- Cell proliferation
- Migration
- Survival
- Angiogenesis (especially via recruitment of pericytes and vascular remodeling)
- Relevance in Cancer Biology
- Overexpression or mutation of PDGFR can drive:
- Tumor angiogenesis
- Stromal proliferation (tumor-supporting environment)
- Autocrine loops that sustain tumor growth
- Seen in:
- Gastrointestinal stromal tumors (GIST) (especially PDGFRA mutations)
- Gliomas
- Leukemias
- Some sarcomas
- Targeted Therapies
- Sunitinib, imatinib, regorafenib, and pazopanib can inhibit PDGFR activity.
- These drugs are used in tumors where PDGFR is mutated or overactive (e.g., GIST).
- Blocking PDGFR can reduce:
- Tumor blood vessel support
- Stromal-tumor interactions
- Direct tumor proliferation (in PDGFR-driven cancers)