Choi Bongkun, Lee Eun-Jin, Song Da-Hyun, Yoon Sung-Chul, Chung Yeon-Ho, Jang Youngsaeng, Kim Sang-Min, Song Youngsup, Kang Sang-Wook, Yoon Seung-Yong, Chang Eun-Ju
Department of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Oncotarget. 2014 Jan 30;5(2):481-92. doi: 10.18632/oncotarget.1664.
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.
五聚体3（PTX3）是肿瘤相关炎症的调节因子，已知其与肿瘤分级和恶性肿瘤的严重程度呈正相关，但其确切作用仍不清楚。本研究发现，在64例人类乳腺癌患者中，与肺、肝和脑转移相比，PTX3在乳腺癌远处骨转移中的表达上调。PTX3表达升高与乳腺癌患者的不良生存相关。PTX3在骨转移性乳腺癌细胞系中的表达也上调，并被促炎细胞因子TNFα进一步增强。给予PTX3可促进乳腺癌细胞的迁移潜能以及巨噬细胞（破骨细胞前体）向乳腺癌细胞的募集。此外，TNFα导致的PTX3表达升高导致破骨细胞形成增加，这意味着PTX3在乳腺癌细胞溶骨性骨转移中具有独特作用。此外，使用PTX3特异性siRNA沉默PTX3可阻止乳腺癌细胞迁移、巨噬细胞趋化以及随后的破骨细胞形成。这些发现为PTX3在乳腺癌炎症相关溶骨性并发症中的关键作用提供了重要见解。
