期刊
CLINICAL & EXPERIMENTAL METASTASIS
卷 18, 期 5, 页码 391-400出版社
KLUWER ACADEMIC PUBL
DOI: 10.1023/A:1010930918055
关键词
CD26; dipeptidyl peptidase IV; invasion; Matrigel; metastasis
类别
资金
- NCI NIH HHS [CA58314] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA058314] Funding Source: NIH RePORTER
Dipeptidyl peptidase IV (DPPIV) is a 110-kD, trans-membrane, ectoenzyme, with ubiquitous expression. DPPIV has numerous functions including involvement in T-cell activation, cell adhesion, digestion of proline containing peptides in the kidney and intestines, HIV infection and apoptosis, and regulation of tumorigenicity in certain melanoma cells. Constitutively expressed on numerous epithelial cell types, DPPIV is often disregulated in a variety of human malignancies. The most striking evidence of DPPIV down-regulation is found in transformed melanocytes, where nearly 100% of melanomas lack DPPIV expression. We have identified DPPIV as a gene that can alter the invasive potential of a number of melanoma cell lines. By transfecting the full-length cDNA of DPPIV, we have established stable melanoma cell lines that express comparable levels of the DPPIV protein as normal epidermal melanocytes. Matrigel invasion assays were utilized to study the effects of DPPIV expression on the invasive potential of these cells. The parental and vector transfectants readily migrated across the Matrigel while the invasiveness of DPPIV transfected cells was reduced by greater than 75%. The effects on cellular invasion are not attributed to overall growth characteristics, as both DPPIV expressing and non-expressing cells behave comparably in culture. We have also constructed mutants of DPPIV that lack either the extra-cellular serine protease activity or the six amino acid cytoplasmic domain. Both mutants were stably expressed in melanoma cells. Matrigel invasion assays performed with cells expressing the two mutant forms of the protein revealed phenotypic effects similar to wild type function. In this study, we have demonstrated that expression of a proteolytically active form of the DPPIV protein inhibits the invasiveness of malignant melanoma cell lines lacking endogenous DPPIV expression. Furthermore, we have shown that neither the protease activity nor the cytoplasmic domain of DPPIV is required for its anti-invasive activity.
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