STEAP1 is overexpressed in cancers: A promising therapeutic target
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Authors: Moreaux, Jerome; Kassambara, Alboukadel; Hose, Dirk; Klein, Bernard
Abstract
The six-transmembrane epithelial antigen of prostate (STEAP) protein was identified in advanced prostate cancer and is up-regulated in multiple cancer cell lines, including prostate, bladder, colon, ovarian, and Ewing sarcoma. STEAP1 was described as a suitable antigen for T-cell-based or antibody-based immunotherapy. We have investigated the expression of STEAP1 in 40 human tumor types - brain, epithelial, lymphoid and in their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. STEAP1 was found significantly overexpressed in 11 cancers. In addition, high STEAP1 expression was associated with poor overall survival in colorectal cancer, diffuse large B cell lymphoma, acute myeloid leukemia and multiple myeloma. Taken together, these data suggest that STEAP1 is a potential therapeutic target for T-cell based immunotherapy or antibody therapy in a large panel of cancers. (C) 2012 Elsevier Inc. All rights reserved.
Identification of Transmembrane Protein in Prostate Cancer by the Escherichia coli Ampicillin Secretion Trap: Expression of CDON Is Involved in Tumor Cell Growth and Invasion
PATHOBIOLOGY
Authors: Hayashi, Tetsutaro; Oue, Naohide; Sakamoto, Naoya; Anami, Katsuhiro; Oo, Htoo Zarni; Sentani, Kazuhiro; Ohara, Shinya; Teishima, Jun; Matsubara, Akio; Yasui, Wataru
Abstract
Aims: Prostate cancer (PCa) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue, and especially related to proteins located on the cell membrane, will be useful molecular markers for diagnosis and may also be good therapeutic targets. The aim of this study was to identify genes that encode transmembrane proteins present in PCa. Methods and Results: We generated Escherichia coli ampicillin secretion trap (CAST) libraries from 2 PCa cell lines and normal prostate tissues. By sequencing 3,264 colonies from CAST libraries, we identified 18 candidate genes that encode transmembrane proteins present in PCa. Quantitative RT-PCR analysis of these candidates revealed that STEAP1, ADAM9 and CDON were expressed much more highly in PCa than in 15 kinds of normal tissues. Among the candidates, CDON encodes the CDO protein, which is an orphan cell surface receptor of the immunoglobulin superfamily. Additional quantitative RT-PCR revealed that 83% of PCa tissues showed CDON overexpression. Knockdown of CDON in DU145 cells induced 5-fluorouracil-induced apoptosis and inhibited invasion ability. Conclusion: These results suggest that CDON has a high potential as a therapeutic target for PCa. Copyright (C) 2011 S. Karger AG, Basel
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