Cancer esearch oenvironment and Immunology s of Osteoclasts Contributes to Development of R eosarcoma Pulmonary Metastases

nloaded conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of last-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS red with nonmalignant bone (P < 0.0001). Moreover, lesions from OS patients with pulmonary metasad 2-fold less ACP5/TRAP expression (P < 0.018) than lesions from patients without metastases. In ad, we found a direct correlation (P = 0.0166) between ACP5/TRAP expression and time to metastasis. ore, we examined whether metastasis-competent (MC) OS cells could induce loss of ACP5 osteoclasts ntribute to metastasis. We found that MC OS cell lines can inhibit osteoclastogenesis in vitro and . In addition, osteoclasts can inhibit the migration of MC OS cells in vitro. Finally, ablation of osteoclasts oledronic acid increases the number of metastatic lung lesions in an orthotopic OS model, whereas rant treatment increases osteoclast numbers and reduces metastatic lesions. These data indicate that fulvest the metastatic potential of OS is determined early in tumor development and that loss of osteoclasts in the primary lesion enhances OS metastasis. Cancer Res; 70(18); 7063–72. ©2010 AACR.