Several recent studies have demonstrated the involvement of cell-surface nucleolin in angiogenesis and tumor growth. In this study, we addressed the following questions:

Does N6L (or Nucant), a synthetic ligand of cell-surface nucleolin (nM range), block angiogenesis and tumor growth? What are its mechanisms of action, its bio-distribution and finally does it target other cell surface nucleolin partner proteins?

The key findings of this study are that:

• N6L inhibits anchorage-dependent and independent growth of several tumor cell lines and blocked angiogenesis

• N6L inhibit, in vivo tumor growth in a number of mouse subcutaneous human xenograft models

• N6L bio-distribution studies indicate that N6L rapidly localizes selectively in tumor tissue (see cover figure)

• N6L is a pro-apoptotic molecule, as demonstrated by in vivo as well as in vitro experiments

• Pull-down experiments and mass-spectrometry analysis have confirmed that nucleophosmin is a partner for nucleolin and also a target (nM range) for N6L

ImmuPharma group is currently developing N6L in Phase I/IIa clinical trials before initiating full efficacy studies in various indications as identified during this series of experiments. We believe that these findings pave the way for a novel approach of cancer treatment. For details, see the article by Destouches and colleagues on page 3296 of this issue.