Anti-CCL23 monoclonal antibody, clone 70634

Objective: To test whether nitric oxide (NO) enhances the cytotoxicity of cisplatin in a head and neck squamous cell carcinoma (HNSCC) cell line. Background: Cisplatin is one of the most frequently used chemotherapeutic agents in the treatment of HNSCC. NO has been shown to play an important role in regulating tumor growth. Previous studies demonstrate that NO can enhance the cytotoxicity of cisplatin in Chinese hamster lung fibroblasts. In this report, we examined the in vitro interaction of NO and cisplatin in a HNSCC cell line. Materials and Methods: CCL23 cells were pretreated with three different NO donors: PAPA/NO (t 1/2 = 15 min), DPTA/NO (t 1/2 = 3 h), and DETA/NO (t 1/2 = 20 h). The cells were rinsed and exposed for 6 hours to a culture medium containing cisplatin. Cell survival and LD50 of cisplatin were calculated with and without NO pretreatment. Results: PAPA/NO and DPTA/NO did not show any cytotoxic activity and did not change the LD50 of cisplatin. DETA/NO when used alone resulted in 25.6% cell death at its peak dose (100 muM). Pretreatment with DETA/NO resulted in almost a threefold reduction of the LD50 of cisplatin (6.8 vs. 2.4 mug/mL). Pretreatment with DETA/NO sensitized the HNSCC cells to subsequent cisplatin activity (two-sided P = .00016). Conclusion: Pretreatment of HNSCC cells with long-acting NO donors enhances cisplatin activity. Short- and medium-acting NO donors do not exert a toxic effect and do not augment the activity of cisplatin. NO agonists should be considered in the future as a possible adjunct to cisplatin in the treatment of HNSCC. Further studies with animal models are necessary to further clarify this relationship.

Human CCL23 (also known as CK beta 8. MPIF-1, or MIP-3) has been recently reported to induce endothelial cell migration and tube formation via CCR1. Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix and also appear to play critical roles in angiogenesis. In the present study, we have demonstrated that CCL23 enhances the expression of MMP-2 mRNA and protein levels in endothelial cells in a dose-dependent manner, but hits no effect on the expression levels of MMP-9, TlMP-1, TIMP2, and MT1-MMP. CCL23 was shown to dose-dependently activate the expression of the MMP-2/Lue reporter gene. thereby indicating that it stimulates the transcription of the MMP-2 gene. Vascular endothelial cells. when exposed to CCL23, showed it marked ability to invade through a 3D Matrigel. This increase in invasion was also correlated with enhancements in the expression and activity of MMP-2. Neutralization with anti-CCL23 and anti-CCR1 antibodies. its well as the heat-induced inactivation of CCL23, resulted in it blockage of the CCL23-activated invasion, indicating that the invasion of HUVECs was induced by CCL23 specifically. Futhermore, we showed that the CCL23-induced invasion was inhibited by MMP inhibitors such as GM6001 and a specific MMP-2 Inhibitor 1. Our results indicate that CCL23 may play a direct role in angiogenesis, via the upregulation of MMP-2 expression. (c) 2005 Elsevier Inc. All rights reserved.