Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function
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Bongkun Choi1,4, Eun-Jin Lee1,4, Da-Hyun Song1,4, Sung-Chul Yoon2, Yeon-Ho Chung1,4, Youngsaeng Jang1,4, Sang-Min Kim1,4, Youngsup Song1,3,4, Sang-Wook Kang1,3,4, Seung-Yong Yoon3,4, and Eun-Ju Chang1,3,4
1 Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
2 Division of Biostatistics, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
3 Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
4 Cellular Dysfunction Research Center and BMIT, University of Ulsan College of Medicine, Seoul, Korea
Eun-Ju Chang, email:
Keywords: breast cancer, PTX3, osteoclast, RANKL, osteolysis.
Received: December 10, 2013 Accepted: January 15, 2014 Published: January 15, 2014
Pentraxin 3 (PTX3), a modulator of tumor-associated inflammation, is known to be positively correlated with tumor grade and severity of malignancies, but its exact role remains unclear. This study found that PTX3 expression was up-regulated in distant bone metastases of breast cancer compared to lung, liver, and brain metastases in 64 human breast cancer patients. Elevated expression of PTX3 was correlated with poor survival in patients with breast cancer. PTX3 expression was also up-regulated in a bone metastatic breast cancer cell line and further enhanced by pro-inflammatory cytokine TNFα. Administration of PTX3 promoted the migratory potential of breast cancer cells and the mobilization of macrophages, a precursor of osteoclasts (OCs), toward breast cancer cells. In addition, elevated expression of PTX3 by TNFα led to enhanced OC formation, implying the distinct role of PTX3 in osteolytic bone metastasis of breast cancer cells. Furthermore, PTX3 silencing using PTX3-specific siRNA prevented breast cancer cell migration, macrophage chemotaxis, and subsequent OC formation. These findings provide an important insight into the key role of PTX3 in inflammation-associated osteolytic complications of breast cancer.
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