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A spliced form of CD44 expresses the unique glycan that is recognized by the prostate cancer specific antibody F77

2017; Impact Journals LLC; Volume: 9; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.23341

1949-2553

Xi Chen, Yasuhiro Nagai, Zhiqiang Zhu, Hang Ruan, Donna M. Peehl, Mark I. Greene, Hongtao Zhang,

RNA Interference and Gene Delivery

// Xi Chen 1, * , Yasuhiro Nagai 1, * , Zhiqiang Zhu 1 , Hang Ruan 1 , Donna M. Peehl 2 , Mark I. Greene 1 and Hongtao Zhang 1 1 Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA 2 Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA * These authors contributed equally to this work Correspondence to: Mark I. Greene, email: greene@reo.med.upenn.edu Hongtao Zhang, email: zhanghon@mail.med.upenn.edu Keywords: prostate cancer; antibody; post-translational modification; O-linked glycosylation; CD44 Received: August 01, 2017 Accepted: November 26, 2017 Published: December 16, 2017 ABSTRACT Prostate cancer is the most common cancer occurring in men in the United States. The monoclonal antibody F77 that was originally developed in our laboratory recognizes mainly glycolipids as well as O-linked glycosylation on proteins in prostate cancer cells. We have identified a spliced form of glycoprotein CD44 as one critical protein expressing the F77 antigen. The F77-specific glycosylation occurs on multiple potential glycosylation sites on the CD44 protein encoded by the fourteenth exon. CD44 is a tumor stem cell marker and is known to induce tumor stemness and metastasis. Knockdown of CD44 or FUT1 genes dramatically reduced F77-induced apoptosis in prostate cancer cell lines. We developed an ELISA using both a CD44 antibody and F77 to identify the special form of glycosylated CD44 from prostate cancer cells as well as from serum samples of prostate cancer patients. These results reveal a CD44-dependent mechanism for F77 to induce tumor cell apoptosis, and a new strategy for the detection of glycosylated CD44 proteins secreted by prostate cancer cells.