Effects of bone morphogenetic protein-2 on proliferation and angiogenesis in oral squamous cell carcinoma.
Experimental data and limited patient experience suggest that rhBMP-2 can be used to regenerate bone in acquired segmental defects of the mandible. Most of these defects are caused by resection of oral squamous cell carcinoma (OSCC) and the biologic effects of rhBMP-2 on these carcinoma cells are unknown. The objective of this study was to determine whether rhBMP-2 produces adverse effects on proliferation and angiogenesis in OSCC, two biologic processes critical to tumor formation. In vitro studies included treating OSCC cells with rhBMP-2 or an adenoviral vector containing the cDNA for BMP-2. In vivo studies involved co-transplantation of OSCC cells with bone marrow stromal cells genetically modified to over express BMP-2, to mimic a clinically relevant scenario for regenerating bone using cell-based therapy in a wound containing microscopic residual disease. Proliferation, as measured by a MTT assay in vitro and tumor growth in vivo was not affected by treatment with BMP-2. Angiogenesis, measured by secretion of the proangiogenic molecules VEGF and IL-8 in vitro and microvessel density in vivo, was not affected. Exposure of OSCC cells to BMP-2 does not stimulate proliferation or angiogenesis. Further studies are needed before using rhBMP-2 for bone tissue engineering in oral cancer-related defects.
Gao
Q
Q
Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan, USA.
Tong
W
W
Luria
J S
JS
Wang
Z
Z
Nussenbaum
B
B
Krebsbach
P H
PH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation / Q000473:pathology; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D016209:Interleukin-8 / Q000032:analysis; D051379:Mice; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D009368:Neoplasm Transplantation / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology*; D017154:Stromal Cells / Q000637:transplantation; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014841:von Willebrand Factor / Q000032:analysis
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D016209:Interleukin-8; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C499469:recombinant human bone morphogenetic protein-2; D014841:von Willebrand Factor