title: EDB Fibronectin Specific Peptide for Prostate Cancer Targeting.
abstract: Extradomain-B fibronectin (EDB-FN), one of the oncofetal fibronectin (onfFN) isoforms, is a high-molecular-weight glycoprotein that mediates cell adhesion and migration. The expression of EDB-FN is associated with a number of cancer-related biological processes such as tumorigenesis, angiogenesis, and epithelial-to-mesenchymal transition (EMT). Here, we report the development of a small peptide specific to EDB-FN for targeting prostate cancer. A cyclic nonapeptide, CTVRTSADC (ZD2), was identified using peptide phage display. A ZD2-Cy5 conjugate was synthesized to accomplish molecular imaging of prostate cancer in vitro and in vivo. ZD2-Cy5 demonstrated effective binding to up-regulated EDB-FN secreted by TGF-β-induced PC3 cancer cells following EMT. Following intravenous injections, the targeted fluorescent probe specifically bound to and delineated PC3-GFP prostate tumors in nude mice bearing the tumor xenografts. ZD2-Cy5 also showed stronger binding to human prostate tumor specimens with a higher Gleason score (GS9) compared to those with a lower score (GS 7), with no binding in benign prostatic hyperplasia (BPH). Thus, the ZD2 peptide is a promising strategy for molecular imaging and targeted therapy of prostate cancer.
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Han
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Zhuxian
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Shi
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Da
authors.initials: D
authors.lastname: Sun
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Cristina
authors.initials: C
authors.lastname: Magi-Galluzzi
authors.affiliation: †Department of Biomedical Engineering and ‡Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106, United States.|§Glickman Urological Institute, and ∥Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44106, United States.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004396:Coloring Agents / Q000737:chemistry; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D061848:Optical Imaging; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013379:Substrate Specificity; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D002232:Carbocyanines; D004396:Coloring Agents; D005353:Fibronectins; D009842:Oligopeptides; D016212:Transforming Growth Factor beta; C085321:cyanine dye 5; C121542:oncofetal fibronectin