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Type: Journal article
Title: Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases
Author: Endo-Munoz, L.
Cumming, A.
Rickwood, D.
Wilson, D.
Cueva, C.
Ng, C.
Strutton, G.
Cassady, A.
Evdokiou, A.
Sommerville, S.
Dickinson, I.
Guminski, A.
Saunders, N.
Citation: Cancer Research, 2010; 70(18):7063-7072
Publisher: Amer Assoc Cancer Research
Issue Date: 2010
ISSN: 0008-5472
Statement of
Liliana Endo-Munoz, Andrew Cumming, Danny Rickwood, Danielle Wilson, Claudia Cueva, Charlotte Ng, Geoffrey Strutton, A. Ian Cassady, Andreas Evdokiou, Scott Sommerville, Ian Dickinson, Alexander Guminski, and Nicholas A. Saunders
Abstract: We conducted a transcriptomic screen of osteosarcoma (OS) biopsies and found that expression of osteoclast-specific tartrate-resistant acid phosphatase 5 (ACP5/TRAP) is significantly downregulated in OS compared with nonmalignant bone (P < 0.0001). Moreover, lesions from OS patients with pulmonary metastases had 2-fold less ACP5/TRAP expression (P < 0.018) than lesions from patients without metastases. In addition, we found a direct correlation (P = 0.0166) between ACP5/TRAP expression and time to metastasis. Therefore, we examined whether metastasis-competent (MC) OS cells could induce loss of ACP5(+) osteoclasts and contribute to metastasis. We found that MC OS cell lines can inhibit osteoclastogenesis in vitro and in vivo. In addition, osteoclasts can inhibit the migration of MC OS cells in vitro. Finally, ablation of osteoclasts with zoledronic acid increases the number of metastatic lung lesions in an orthotopic OS model, whereas fulvestrant treatment increases osteoclast numbers and reduces metastatic lesions. These data indicate that the metastatic potential of OS is determined early in tumor development and that loss of osteoclasts in the primary lesion enhances OS metastasis.
Keywords: Osteoclasts
Mice, Inbred BALB C
Bone Neoplasms
Lung Neoplasms
Acid Phosphatase
Middle Aged
Young Adult
Tartrate-Resistant Acid Phosphatase
Rights: ©2010 American Association for Cancer Research
DOI: 10.1158/0008-5472.CAN-09-4291
Appears in Collections:Animal and Veterinary Sciences publications
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