Identification of a novel gelsolin truncate in the vertical and metastatic phase malignant melanomas

Examination of 38 human melanoma samples by Western blotting analysis with anti-gelsolin antibodies showed that a new 85 kDa truncated gelsolin (GSNp85), co-expressed with wild-type gelsolin, was frequently expressed in vertical growth phase melanomas (Clark level II-IV) and metastatic growth phase melanomas. The GSNp85 truncate was not expressed in radial growth phase melanomas (Clark level I), acquired naevi, other skin cancers or normal skin tissues. Peptide-sequencing analysis revealed that GSNp85 lacks the C-terminal domain of wild-type gelsolin at the region containing the caspase-8 recognition site IETD. Caspase-8 processing was detected in GSNp85-positive but not GSNp85-negative melanomas. These data suggest that GSNp85 is a cleavage product of caspase-8 and may be useful as a new marker for the vertical or metastatic growth phase of malignant melanoma.