Chemokine Decoy Receptor D6 Plays a Negative Role in Human Breast Cancer

• Published in: Molecular cancer research Vol. 6; no. 8; pp. 1276 - 1288
• Main Authors: Wu, Feng-Ying, Ou, Zhou-Luo, Feng, Lan-Yun, Luo, Jian-Min, Wang, Lei-Ping, Shen, Zhen-Zhou, Shao, Zhi-Min
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.08.2008
• Subjects: Animals; breast cancer; Breast Neoplasms - blood supply; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Cell Line, Tumor; Cell Proliferation - drug effects; Chemokine decoy receptor D6; Chemokine Receptor D6; Chemokines - genetics; Chemokines - metabolism; DNA, Complementary - genetics; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Interleukin-1beta - pharmacology; Lymphatic Metastasis - pathology; metasatsis; Mice; Middle Aged; Neoplasm Invasiveness; Neoplasm Transplantation; Neovascularization, Pathologic - metabolism; Receptors, CCR10 - genetics; Receptors, CCR10 - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Survival Rate; Transfection; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-07-2108

Chemokine binding protein D6 is a promiscuous decoy receptor that can inhibit inflammation in vivo ; however, the role it plays in cancer is not well known yet. In this study, we showed for the first time that human breast cancer differentially expressed D6 and the expression could be regulated by some cytokines. More importantly, overexpression of D6 in human breast cancer cells inhibits proliferation and invasion in vitro and tumorigenesis and lung metastasis in vivo . This inhibition is associated with decreased chemokines (e.g., CCL2 and CCL5), vessel density, and tumor-associated macrophage infiltration. Furthermore, D6 expression is inversely correlated to lymph node metastasis as well as clinical stages, but positively correlated to disease-free survival rate in cancer patients. Therefore, D6 plays a negative role in the growth and metastasis of breast cancer. (Mol Cancer Res 2008;6(8):1276–88)