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.
Highlights
Prostate cancer is the most common cancer in men and one of the leading causes of cancer-related death in the United States [1]
The present studies have focused on CD44 standard (CD44s), a transmembrane glycoprotein that is important for cell signaling and tumor stemness and metastasis [17, 18]
In the prostate cancer cell line PC3, an isoform of CD44 with the molecular weight of 85–90 kDa was predominantly precipitated by monoclonal antibody (mAb) F77 (Figure 1A and Supplementary Figure 1)
Summary
Prostate cancer is the most common cancer in men and one of the leading causes of cancer-related death in the United States [1]. Serum prostate-specific antigen (PSA) has been used as a biomarker to screen for prostate cancer, measurement issues lead to over-diagnosis, resulting in overtreatment of prostate lesions that do not necessarily require therapy [2]. Tumor cell-specific antibodies such as anti-CD20 (rituximab) and anti-erbB2/neu (trastuzumab) antibodies have proven to be effective in clinical cancer treatment [4, 5]. These targeted therapeutic antibodies have inhibitory effects on tumor cells by binding to targeted molecules, and lead to heightened host immunity against tumors [6]. We demonstrated that anti-erbB2/neu targeted antibody can promote the development of tumor specific CD8+ T cells in a syngeneic MMTV-neu mouse model [7]
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