Dipeptidyl peptidase-IV (DPP-IV) represents a unique proteolytic activity cleaving N-terminal X-Pro dipeptides. In addition to canonical DPP-IV/CD26, a number of other molecules have been discovered which exhibit DPP-IV-like enzymatic activity and various degree of structural similarity. These comprise enzymatically active fibroblast activation protein-alpha, DPP-II, DPP8, DPP9 and enzymatically inactive DPP6 and DPP10 that have been grouped as "DPP-IV activity and/or structure homologues" (DASH). Because the enzymatically active DASH can share similar sets of biologically active substrates and are frequently coexpressed within single cell or on tissue level, it is tempting to consider their participation on biological function(s) previously attributed to DPP-IV/CD26. It is speculated that disrupted expression and enzymatic activity of some DASH might corrupt the message carried by their substrates, with consequent promotion of abnormal cell behavior. Thus, modulation of activity of a particular enzyme using e.g. inhibitors, specific antibodies or modifying its expression may be an attractive therapeutic concept in cancer treatment. This review summarizes current knowledge of the expression and possible function of DPP-IV enzymatic activity bearing molecules in human brain tumors.

Laboratory of Cancer Cell Biology Department of Biochemistry and Experimental Oncology 1st Faculty of Medicine Charles University Prague Institute of Physiology Academy of Sciences Czech Republic

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Fibroblast activation protein alpha is expressed by transformed and stromal cells and is associated with mesenchymal features in glioblastoma