The role of CD26/dipeptidyl peptidase IV in cancer

Abstract

CD26/DPPIV is a multifunctional cell surface protein that is widely expressed in most cell types including T lymphocytes, on which it is a marker of activation. It is also present in serum and other body fluids in a truncated form (sCD26/DPPIV). It preferentially cleaves N-terminal dipeptides from polypeptides with proline or alanine in the penultimate position, and in doing so, regulates the activities of a number of cytokines and chemokines. Due in part to this ability to regulate the activity of biopeptides, it can act as a tumor suppressor or activator. It can associate with several proteins, among them fibroblast activating protein-alpha (FAP-alpha), plasminogen, adenosine deaminase (ADA), the tyrosine phosphatase CD45, and the chemokine receptor CXCR4. It can also bind to the extracellular matrix (ECM) and depending on the presence of other ligands, this process can either lead to increased or decreased invasive activity of the cells on which it is expressed. As a result of these characteristics, CD26/DPPIV plays an important role in tumor biology, and is useful as a marker for various cancers, with its levels either on the cell surface or in the serum being increased in some neoplasms and decreased in others. Our group has shown that CD26/DPPIV can be manipulated by such agents as CD26 cDNA-carrying plasmids, siRNA and monoclonal antibodies, resulting in both in vitro and in vivo inhibition of cell growth, enhanced sensitivity to selected chemotherapeutic agents, and enhanced survival of mouse xenograft models. These studies have demonstrated the utility of these tools as potential targeted therapies for specific cancers expressing CD26/DPPIV.

Emerging roles of serine proteinases in tissue turnover in arthritis

“…DPP-2 is lysosomal (106), whereas DPP-4 and FAP␣ are both type II transmembrane proteins with a large C-terminal extracellular domain, a transmembrane domain, and a short cytoplasmic tail (107,108). These enzymes have the unique proteolytic ability to cleave N-terminal dipeptides from proteins with proline or alanine in the penultimate position.…”

Ascites in Ovarian Cancer Progression: Opportunities for Biomarker Discovery and New Avenues for Targeted Therapies

“…Once these cells accumulate in ascites they can be "educated" by growth factors and cytokines in the surrounding environment to support tumor growth [19]. Upon stimulation by ascites, myoibroblastic-like cells have been shown to produce dipeptidyl peptidase IV [35], which is a multifunctional protein that have been associate with tumor growth in some context [36]. Exposure of myoibroblastic-like cells to ascites increased the secretion of VEGF and other pro-survival soluble factors [19,37].…”

Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines

“…It has been reported to be expressed in various other tissues, placenta, kidney, lung, brain, liver, endothelium, and intestines (16)(17)(18)(19). CD26 also plays a role in tumor development and its expression was reported in various human malignancies, mainly cancers of thyroid, breast, prostate, and ovary (13,20). We immunohistochemically evaluated the expression of CD26 in mesothelioma in determining the proper selection criteria of the mesothelioma patients for humanized monoclonal anti-CD26 antibody treatment.…”