Cell surface Thomsen-Friedenreich proteome profiling of metastatic prostate cancer cells reveals potential link with cancer stem cell-like phenotype.

// Feng Li 1, 2, * , Olga V. Glinskii 1, 3, * , Brian P. Mooney 4 , Kate Rittenhouse-Olson 5, 6 , Kenneth J. Pienta 7 and Vladislav V. Glinsky 1, 2 1 Research Service, Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA 2 Department of Pathology and Anatomical Sciences, University of Missouri, School of Medicine, Columbia, MO, USA 3 Department of Medical Pharmacology and Physiology, University of Missouri, School of Medicine, Columbia, MO, USA 4 Department of Biochemistry and Charles W. Gehrke Proteomics Center, University of Missouri-Columbia, Columbia, MO, USA 5 Department of Biotechnical and Clinical Laboratory Sciences and the Department of Microbiology, University at Buffalo, Buffalo, NY, USA 6 For-Robin, Inc, Buffalo, NY, USA 7 Department of Urology, The James Buchanan Brady Urological Institute, Departments of Oncology and Pharmacology and Molecular Sciences, The Johns Hopkins School of Medicine, Baltimore, MD, USA * These authors contributed equally to this work Correspondence to: Vladislav V. Glinsky, email: glinskiivl@health.missouri.edu Keywords: Thomsen-Friedenreich antigen, proteomics, tumor metastasis, cancer stem cells, prostate cancer Received: June 02, 2017 Accepted: September 29, 2017 Published: October 20, 2017 ABSTRACT The tumor-associated Thomsen-Friedenreich glycoantigen (TF-Ag) plays an important role in hematogenous metastasis of multiple cancers. The LTQ Orbitrap LC-MS/MS mass spectrometry analysis of cell surface TF-Ag proteome of metastatic prostate cancer cells reveals that several cell surface glycoproteins expressing this carbohydrate antigen in prostate cancer (CD44, α2 integrin, β1 integrin, CD49f, CD133, CD59, EphA2, CD138, transferrin receptor, profilin) are either known as stem cell markers or control important cancer stem-like cell functions. This outcome points to a potential link between TF-Ag expression and prostate cancer stem-like phenotype. Indeed, selecting prostate cancer cells for TF-Ag expression resulted in the enrichment of cells with stem-like properties such as enhanced clonogenic survival and growth, prostasphere formation under non-differentiating and differentiating conditions, and elevated expression of stem cell markers such as CD44 and CD133. Further, the analysis of the recent literature demonstrates that TF-Ag is a common denominator for multiple prostate cancer stem-like cell populations identified to date and otherwise characterized by distinct molecular signatures. The current paradigm suggests that dissemination of tumor cells with stem-like properties to bone marrow that occurred before surgery and/or radiation therapy is largely responsible for disease recurrence years after radical treatment causing a massive clinical problem in prostate cancer. Thus, developing means for destroying disseminated prostate cancer stem-like cells is an important goal of modern cancer research. The results presented in this study suggest that multiple subpopulation of putative prostate cancer stem-like cells characterized by distinct molecular signatures can be attacked using a single target commonly expressed on these cells, the TF-Ag.