Stromal cell-derived factor-1α-induced cell proliferation and its possible regulation by CD26/dipeptidyl peptidase IV in endometrial adenocarcinoma

CD26/dipeptidylpeptidase IV (DPPIV) is a 110 kD membrane-bound extracellular peptidase with ubiquitous expressions, and has a variety of functional properties in the development of human malignancies as well as T-cell biology. According to recent reports, stromal cell derived factor-1α (SDF-1α), which is a good substrate for CD26/DPPIV, is expressed in various solid tumors and is involved in tumor development or metastasis. We investigated the expression of SDF-1α and its corresponding receptor, CXCR4, in human endometrial carcinoma (EMCA) tissues and the function of SDF-1α on EMCA cells with its regulation by CD26/DPPIV. We demonstrated that SDF-1α and CXCR4 were expressed in human EMCA, and these immunoreactivities were significantly low in Grade 3 EMCA, which was similar to that of CD26/DPPIV, compared to those in Grade 1 and Grade 2. Additionally, exogenous SDF-1α concentration was significantly lower in CD26/DPPIV-transfected EMCA cells than that in vector-transfected cells. Moreover, exogenous SDF-1α significantly stimulated cell proliferation in vector-transfected cells in a concentration dependent manner. In contrast, in CD26/DPPIV-transfected cells, there was no apparent effect on proliferation shown by the addition of exogenous SDF-1α. This is the first report showing a direct link between the SDF-1α/CXCR4 pathway with CD26/DPPIV in solid tumors, suggesting that CD26/DPPIV is likely to directly modulate various SDF-1α induced functions.