Elevated Pentraxin 3 in bone metastatic breast cancer is correlated with osteolytic function.
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.
Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Bongkun
B
Choi
Eun-Jin
EJ
Lee
Da-Hyun
DH
Song
Sung-Chul
SC
Yoon
Yeon-Ho
YH
Chung
Youngsaeng
Y
Jang
Sang-Min
SM
Kim
Youngsup
Y
Song
Sang-Wook
SW
Kang
Seung-Yong
SY
Yoon
Eun-Ju
EJ
Chang
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008822:Mice, Transgenic; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology; D000683:Serum Amyloid P-Component / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D000099153:Pentraxins
D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins