Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases

Endo-Munoz, Liliana, Cumming, Andrew, Rickwood, Danny, Wilson, Danielle, Cueva, Claudia, Ng, Charlotte, Strutton, Geoffrey, Cassady, A. Ian, Evdokiou, Andreas, Sommerville, Scott, Dickinson, Ian, Guminski, Alexander and Saunders, Nicholas A. (2010) Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases. Cancer Research, 70 18: 7063-7072. doi:10.1158/0008-5472.CAN-09-4291

Author Endo-Munoz, Liliana
Cumming, Andrew
Rickwood, Danny
Wilson, Danielle
Cueva, Claudia
Ng, Charlotte
Strutton, Geoffrey
Cassady, A. Ian
Evdokiou, Andreas
Sommerville, Scott
Dickinson, Ian
Guminski, Alexander
Saunders, Nicholas A.
Title Loss of osteoclasts contributes to development of osteosarcoma pulmonary metastases
Journal name Cancer Research   Check publisher's open access policy
ISSN 0008-5472
Publication date 2010-09-15
Sub-type Article (original research)
DOI 10.1158/0008-5472.CAN-09-4291
Volume 70
Issue 18
Start page 7063
End page 7072
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher American Association for Cancer Research
Collection year 2011
Language eng
Formatted 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. ©2010 AACR.
Keyword Resistant acid-phosphatase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Official 2011 Collection
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Created: Thu, 24 Feb 2011, 15:21:43 EST by Kylie Hengst on behalf of UQ Diamantina Institute