VEGF and BMP expression in mouse osteosarcoma cells.
Osteosarcoma is the most common primary bone malignancy. Despite improvements in therapy, approximately 30% of patients experience pulmonary metastasis. Expression of several growth factors, including VEGF and BMPs, has been implicated in tumor progression and metastatic potential. We hypothesized increased metastatic potential of mouse osteosarcoma cells positively correlates with the expression of VEGF and BMPs. We studied the expression patterns of these growth factors in two murine osteosarcoma cell lines with varying degrees of metastatic potential: K7M2 (highly metastatic) and K12 (minimally metastatic). Expression of VEGF and BMP2 were higher in the metastatic K7M2 cell line. We also investigated the effects of the BMP antagonist noggin on osteosarcoma growth characteristics in vitro. We noted decreased motility, altered morphology, and increased cell death in the highly metastatic K7M2 cell line. Less metastatic K12 cells showed substantial cell death without clear alteration of motility or morphology. These data suggest BMP2 expression may be an important factor in osteosarcoma metastasis and noggin administration theoretically could block its actions. Inhibition of BMPs and VEGF should be investigated further as a possible strategy for decreasing the incidence of pulmonary metastases in osteosarcoma.
Weiss
Kurt R
KR
Stem Cell Research Center, Children's Hospital of Pittsburgh and Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Cooper
Gregory M
GM
Jadlowiec
Julie A
JA
McGough
Richard L
RL
Huard
Johnny
J
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D051379:Mice; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D042461:Vascular Endothelial Growth Factor A