1. ¹Department of Oncology, Shanghai Medical College, Cancer Hospital, Breast Cancer Institute, Fudan University, Shanghai, China
2. ²Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai, China

Correspondence: Dr Z-M Shao, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Breast Cancer Institute, Fudan University, 399 Ling-Ling Road, Shanghai 200032, PR China. E-mail: zhimingshao@yahoo.com; Dr J Ding, Shanghai Institute of Material Medica, Chinese Academy of Sciences, Shanghai 200032, PR China

³These co-authors contributed equally to the work.

Received 2 December 2005; Revised 18 April 2006; Accepted 19 April 2006; Published online 19 June 2006.

Abstract

In addition to the role in regulating leukocyte trafficking, chemokines recently have been shown to be involved in cancer growth and metastasis. Chemokine network in tumor neovascularity may be regulated by decoy receptors. Duffy antigen receptor for chemokines (DARC) is a specific decoy receptor binding with the angiogenic CC and CXC chemokines. To investigate the effects of DARC on the tumorigenesis and the metastasis potential of human breast cancer cells, human DARC cDNA was reintroduced into the MDA-MB-231 and MDA-MB-435HM cells which have a high capability of spontaneous pulmonary metastasis. We demonstrated that DARC overexpression induced inhibition of tumorigenesis and/or metastasis through interfering with the tumor angiogenesis in vivo. This inhibition is associated with decreasing CCL2 protein levels, and MVD and MMP-9 expression in xenograft tumors. In human breast cancer samples, we also demonstrated that low expression of the DARC protein is significantly associated with estrogen receptor (ER) status, MVD, lymph node metastasis, distant metastasis and poor survival. Our results suggest for the first time that DARC is a negative regulator of growth in breast cancer, mainly by sequestration of angiogenic chemokines and subsequent inhibition of tumor neovascularity.