Postoperative progression of pulmonary metastasis in osteosarcoma.

Early relapse with distant metastasis often is observed in patients with cancer after resection of the primary tumor. It is considered that resection of the primary tumor induces activation of systemic angiogenesis and enhances progression of remote metastasis. The authors show that resection of the primary osteosarcoma tumor enhances progression of pulmonary metastasis in animal osteosarcoma models. Matrigel plug neovascularization assay revealed that systemic angiogenic activity was elevated after primary tumor removal (tumor intact group, 1.61 +/- 0.21 g/dL; tumor removed group, 4.92 +/- 0.35 g/dL). In addition, serum concentration of the angiogenesis inhibitor, endostatin, decreased significantly after primary tumor removal. Treatment with the antiangiogenic reagent TNP-470 suppressed postoperative progression of pulmonary metastasis. These results indicate the possibility that activation of angiogenic activity after resection of osteosarcoma tumors enhances progression of pulmonary metastasis. The current data also suggest that administration of antiangiogenic reagents can prevent progression of pulmonary metastasis in osteosarcoma postoperatively.