Our studies of the interactions of chemokines with epithelial tumor cells show that some tumor cells produce chemokines, while some express receptors for chemokines and are chemoattracted by them. Moreover, some tumor cell types are stimulated to proliferate by chemokines. Furthermore some organs produce chemotactic factors that attract metastatic T cell tumor variants. Purification studies have implicated several chemokines namely RANTES and JE/MCP1 as possible contributors to the metastatic spread of these tumor cells. In addition, a metastatic tumor variant produces factor(s) promoting their own mobility. We plan to further identify these tumor cell attractants and motility promoters and to establish whether they are playing a role in the metastatic process. Several of the chemokines (e.g., MCP-1 and IL-8) have been reported to enhance tumor immune responses. Since dendritic cells (DC), the most effective antigen presenting cell (APC), contribute to tumor immunity, we just completed a study of the effects of chemokines on DC. A number of the C-C chemokines (e.g., MCP-1, MCP-2, MCP-3, MIP1a and RANTES) are chemotactic for human DC, suggesting that they may contribute to the mobilization of these potent APC. We plan to exploit these observations by studying the immune response to murine tumors transfected with the most potent chemoattractants of DC. Studies also have been initiated to develop mutated variants and peptide analogues of chemokines and their receptors. These experiments have only generated weak antagonists to date. The possibility that some anti-inflammatory plant extracts may contain natural inhibitors of proinflammatory chemoattractants is also being evaluated. Some components in extracts of Aloe contain inhibitors of chemokines. Most recently we have initiated studies to establish whether HIV-1 envelope proteins interfere with chemokines. In fact, gp120 can competitively inhibit the binding of MIP1a and RANTES to human monocytes. Further purification and characterization studies are needed to identify the responsible molecular entities. AIDS TITLE: Identification of chemokine antagonists in HIV-1 envelope proteins.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
Project #
Application #
Study Section
Special Emphasis Panel (LMI)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
National Cancer Institute Division of Basic Sciences
United States
Zip Code
Liu, Ying; Chen, Keqiang; Wang, Chunyan et al. (2013) Cell surface receptor FPR2 promotes antitumor host defense by limiting M2 polarization of macrophages. Cancer Res 73:550-60
Liu, Mingyong; Zhao, Jianhua; Chen, Keqiang et al. (2012) G protein-coupled receptor FPR1 as a pharmacologic target in inflammation and human glioblastoma. Int Immunopharmacol 14:283-8
Bian, Xiu-wu; Jiang, Xue-feng; Chen, Jian-hong et al. (2006) Increased angiogenic capabilities of endothelial cells from microvessels of malignant human gliomas. Int Immunopharmacol 6:90-9
Chen, Keqiang; Iribarren, Pablo; Hu, Jinyue et al. (2006) Activation of Toll-like receptor 2 on microglia promotes cell uptake of Alzheimer disease-associated amyloid beta peptide. J Biol Chem 281:3651-9
Bian, Xiu-wu; Wang, Qing-liang; Xiao, Hua-liang et al. (2006) Tumor microvascular architecture phenotype (T-MAP) as a new concept for studies of angiogenesis and oncology. J Neurooncol 80:211-3
Iribarren, Pablo; Zhou, Ye; Hu, Jinyue et al. (2005) Role of formyl peptide receptor-like 1 (FPRL1/FPR2) in mononuclear phagocyte responses in Alzheimer disease. Immunol Res 31:165-76
Zhou, Ye; Bian, Xiuwu; Le, Yingying et al. (2005) Formylpeptide receptor FPR and the rapid growth of malignant human gliomas. J Natl Cancer Inst 97:823-35
Chen, Keqiang; Iribarren, Pablo; Gong, Wanghua et al. (2005) The essential role of phosphoinositide 3-kinases (PI3Ks) in regulating pro-inflammatory responses and the progression of cancer. Cell Mol Immunol 2:241-52
Zhang, Ning; Inan, Saadet; Inan, Sadeet et al. (2005) A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1. Proc Natl Acad Sci U S A 102:4536-41
Sun, Ronghua; Gao, Ping; Chen, Lin et al. (2005) Protein kinase C zeta is required for epidermal growth factor-induced chemotaxis of human breast cancer cells. Cancer Res 65:1433-41

Showing the most recent 10 out of 35 publications