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

Mesothelioma, a highly aggressive cancer with poor prognosis and refractoryto currently available therapies show increasing trends of its incidence in Japanand other developing countries. Although surgery is a gold standard for patientswith early mesothelioma, most patients with advanced disease are not suitablefor surgical resection and have option of palliative chemotherapy alone. One ofthe new treatment strategies for mesothelioma, the humanized anti-CD26 monoclonalantibody therapy is under development. CD26, a 110-kDa transmembrane glycoproteinwith known dipeptidyl peptidase IV activity, plays a role in tumor developmentand its expression was reported in various human malignancies. This study determinedthe preliminary selection criteria for humanized monoclonal anti-CD26 antibodytherapy. Eighty-one epithelioid (49 differentiated and 32 less differentiated),34 sarcomatoid, 19 biphasic mesothelioma and 8 mesothelioma cell lines were immunohistochemicallyexamined using 8 different commercially available anti-CD26 antibodies for membranousand cytoplasmic expression. The cytoplasmic expression of CD26 was observed inall histological types of mesothelioma, while the membranous expression of CD26was found in 88% of differentiated and 69% of less differentiated epithelioidmesothelioma, and none of sarcomatoid mesothelioma with anti-CD26 antibodies withrabbit polyclonal anti-DPP4 antibody and similar results were also obtained withgoat polyclonal anti-DPP4/CD26 antibody. These antibodies absorbed with solublehuman CD26 proteins do not show CD26 expression in mesothelioma tissue, suggestingthese two antibodies localize true CD26 protein. Seven mesothelioma cell lines,including sarcomatoid types, also showed membranous expression of CD26 in cellblockpreparation. CD26 vector transfection to CD26-negative MSTO-211H cells showedmembranous expression of CD26 by flow cytometry, but not in tumor developed inNOD/SCID mice with inoculation of CD26 vector transfected MSTO-211H cells. Wefound that both rabbit and goat polyclonal antibodies are suitable for immunohistochemicalevaluation of membranous expression of CD26 in mesothelioma.