![]() ![]() Among all known regulatory signaling molecules, the platelet-derived growth factor-BB (PDGF-BB)-platelet-derived growth factor receptor p (PDGFRp) axis is probably the best-characterized signaling system for perivascular cell recruitment6 11. Pericyte coverage on microvessels is regulated by multiple signaling molecules that are produced by endothelial cells and other cell types10. Perivascular cells are often tightly associated with vascular endothelial cells and modulate vascular functions by stabilizing vascular networks, promoting vessel maturation and stability, preventing excessive sprouting, preventing uncontrollable leakage, and modulation of blood perfusion4-9. Consequently, TME is probably the richest source of various signaling molecules that often become activated and execute their biological functions on various cell types3.Ĭorrespondence: Yihai Cao of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm 171 77, SwedenĢCentralResearch Laboratory, The Affiliated Hospitalof Qingdao University,įull list of author information is available at the end of the article These various cells communicate to each other through cell-cell interactions and production of various growth factors and cytokines2. The tumor microenvironment (TME) is constituted of the extracellular matrix and various cellular components including malignant cells, stromal fibroblasts, inflammatory cells, immune cells, vascular endothelial cells, and perivascular cells1' 2. Our study identifies a novel mechanism by which the FGF-2 and PDGF-BB collaboratively modulate perivascular cell coverage in tumor vessels, thus providing mechanistic insights of pericyte-endothelial cell interactions in TME and conceptual implications for treatment of cancers and other diseases by targeting the FGF-2-FGFR-pericyte axis. Thus, FGF-2 directly and indirectly stimulates pericyte proliferation and recruitment by modulating the PDGF-PDGFRP signaling. To ensure activation of PDGFR^, the FGF-2-FGFR1-siganling induces PDGF-BB and PDGF-DD, two ligands for PDGFR^, in angiogenic endothelial cells. FGF-2 sensitizes the PDGFRP signaling through increasing PDGFRP levels in pericytes. Mechanistically, FGF-2 binds to FGFR2 to stimulate pericyte proliferation and orchestrates the PDGFRP signaling for vascular recruitment. Here we show using mice models that FGF-2 is a potent pericyte-stimulating factor in tumors. Perivascular cells are important cellular components in the tumor microenvironment (TME) and they modulate vascular integrity, remodeling, stability, and functions. Kayoko Hosaka, Yunlong Yang, Masaki Nakamura, Patrik Andersson, Xiaojuan Yang, Yin Zhang, Takahiro Seki, 1 1 ") 1 /1 Martin Scherzer, Olivier Dubey, Xinsheng Wang and Yihai Cao , Cell Discovery 20184:3 DOI 10.1038/s4142-1ĭual roles of endothelial FGF-2-FGFR1-PDGF-BB and perivascular FGF-2-FGFR2-PDGFRß signaling pathways in tumor vascular remodeling This solution can then be diluted into other aqueous buffers.Hosaka et al. Reconstitute in 5 mM Tris, pH 7.6 to a concentration of 0.1-1.0 mg/mL. Lyophilized from a 1 mg/ml solution of 5 mM Tris pH 7.6 plus 150 mM NaCl.Ĭentrifuge the vial prior to opening. It is also referred to as BFGF (basic fibroblast growth factor). The recombinant human FGF-2 is a 17.2kDa protein containing 154 amino acid residues. FGF-2 is a basic heparin binding growth factor. The gene FGF2 (fibroblast growth factor 2) is mapped to human chromosome 4q28. The FGF2 mRNA is a target of miRNA miR-503. High levels of FGF2 are present in the kidney of children with HIV (human immunodeficiency virus)-renal diseases. FGF2 is known to stimulate angiogenesis and is associated with cancer development. It plays an important role in spinal cord injury repair. FGF2 also determines the fate of neural precursor cells and promotes neuronal axon regeneration. It stimulates the proliferation of a wide variety of cells including mesenchymal, neuroectodermal and endothelial cells. in growing embryonic neural stem/progenitor cells (NSPCs) in a 2D cultureįGF2 (fibroblast growth factor 2)-human has been used in endothelial colony assay.įGF2 (fibroblast growth factor 2, also referred to as BFGF (basic fibroblast growth factor)) interacts with FGFR1 (fibroblast growth factor receptor 1), FGFR2 and FGFR3.as a component in the neurobasal growth medium.as medium supplement for E9.5 neuroepithelial cell culture. ![]()
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