Development of a small peptide, Box-5, antagonising the effects of Wnt-5a
In contrast to the previously discussed situation in breast cancer it was shown that increased Wnt-5a protein expres-sion in malignant melanoma cells was indicative of a more malignant tumour.
Consequently, if one seeks to use Wnt-5a as a drug target to impair metastasis, different strategies have to be employed for different forms of tumours.
The general idea would then be to either reconstitute Wnt-5a signalling or to block Wnt-5a signalling in a tumour specific manner. The most extensively studied example of a tumour that could be treated by blocking Wnt-5a signalling is malignant melanoma.
Dr. Andersson’s research group has set up a malignant melanoma cell model to study the effects of different Wnt-5a-derived peptides. We use the human malignant melanoma A2058 cell line that lacks endogenous expression of Wnt-5a. By stimulating these melanoma cells with recombinant Wnt-5a we could screen for specific Wnt-5a-derived peptides that blocked the Wnt-5a-induced migration. Using this approach we identified Box-5 as having such properties. This peptide is from here on referred to as Box-5.
The effect of Box-5 is totally opposite to the effect of the Foxy-5 agonist. We will further characterize the mechanisms by which the Box-5 antagonist functions and explore its ability to impair malignant melanoma cell migration and metastasis in vivo.