Role of bone morphogenetic protein 2 in the crosstalk between endothelial progenitor cells and mesenchymal stem cells.
In recent studies, we and others have demonstrated that bone morphogenetic protein-2 (BMP-2) promotes vascularization, inhibits hypoxic cell death of cancer cells and may be involved in tumor angiogenesis. The activation of circulating endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) represents a crucial factor in the process of postnatal neovascularization. BMP-2 protein expression has been detected in several tumor tissues and BMP receptors are expressed in EPCs and MSCs. We therefore analysed the influence of recombinant human (rh) BMP-2 on the function of human EPCs and human bone marrow derived MSCs. Treatment of EPCs isolated from peripheral blood with rhBMP-2 did not induce any significant changes in EPC viability but induced a dose-dependent activation of chemotaxis. Incubation of human MSCs isolated from bone marrow aspirates with rhBMP-2 revealed no significant effect on MSC proliferation. Incubation of EPCs with supernatants of MSCs significantly increased the cell viability compared to controls cultivated with endothelial cell medium. Protein and mRNA expression of the vascular endothelial growth factor (VEGF) family member, placental growth factor (PlGF), which is known to be involved in the expansion and recruitment of EPCs, was induced in MSCs after treatment with rhBMP-2. We conclude that tumor- associated BMP-2 secretion might promote tumor angiogenesis by chemotactic effects on EPCs circulating in the peripheral blood and by increased secretion of paracrine angiogenic growth factors including PlGF in MSCs of the tumor stroma.
Raida
M
M
Department of Hematology and Oncology, University of Leipzig, D-04103 Leipzig, Germany. martin.raida@medizin.uni-leipzig.de
Heymann
A C
AC
Günther
C
C
Niederwieser
D
D
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; C000608036:PGF protein, human; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor