دورية أكاديمية
أعرض في EDS

An interleukin 13 receptor α 2-specific peptide homes to human Glioblastoma multiforme xenografts.

التفاصيل البيبلوغرافية
العنوان: An interleukin 13 receptor α 2-specific peptide homes to human Glioblastoma multiforme xenografts.
المؤلفون: Pandya H; Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. debinski@wfubmc.edu, Gibo DM, Garg S, Kridel S, Debinski W
المصدر: Neuro-oncology [Neuro Oncol] 2012 Jan; Vol. 14 (1), pp. 6-18. Date of Electronic Publication: 2011 Sep 26.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 100887420 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-5866 (Electronic) Linking ISSN: 15228517 NLM ISO Abbreviation: Neuro Oncol Subsets: MEDLINE
أسماء مطبوعة: Publication: 2010- : Oxford : Oxford University Press
Original Publication: 1999-<2002> : Charlottesville, VA : Carden Jennings Pub.,
مواضيع طبية MeSH: Blood-Brain Barrier* , Peptide Library*, Brain Neoplasms/*metabolism , Glioblastoma/*metabolism , Interleukin-13 Receptor alpha2 Subunit/*metabolism , Peptides/*pharmacokinetics, Animals ; Binding, Competitive ; Female ; Humans ; Mice ; Mice, Nude ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
مستخلص: Interleukin 13 receptor α 2 (IL-13Rα2) is a glioblastoma multiforme (GBM)-associated plasma membrane receptor, a brain tumor of dismal prognosis. Here, we isolated peptide ligands for IL-13Rα2 with use of a cyclic disulphide-constrained heptapeptide phages display library and 2 in vitro biopanning schemes with GBM cells that do (G26-H2 and SnB19-pcDNA cells) or do not (G26-V2 and SnB19-asIL-13Rα2 cells) over-express IL-13Rα2. We identified 3 peptide phages that bind to IL-13Rα2 in cellular and protein assays. One of the 3 peptide phages, termed Pep-1, bound to IL-13Rα2 with the highest specificity, surprisingly, also in a reducing environment. Pep-1 was thus synthesized and further analyzed in both linear and disulphide-constrained forms. The linear peptide bound to IL-13Rα2 more avidly than did the disulphide-constrained form and was efficiently internalized by IL-13Rα2-expressing GBM cells. The native ligand, IL-13, did not compete for the Pep-1 binding to the receptor and vice versa in any of the assays, indicating that the peptide might be binding to a site on the receptor different from the native ligand. Furthermore, we demonstrated by noninvasive near infrared fluorescence imaging in nude mice that Pep-1 binds and homes to both subcutaneous and orthotopic human GBM xenografts expressing IL-13Rα2 when injected by an intravenous route. Thus, we identified a linear heptapeptide specific for the IL-13Rα2 that is capable of crossing the blood-brain tumor barrier and homing to tumors. Pep-1 can be further developed for various applications in cancer and/or inflammatory diseases.
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معلومات مُعتمدة: R01 CA74145 United States CA NCI NIH HHS
المشرفين على المادة: 0 (Interleukin-13 Receptor alpha2 Subunit)
0 (Peptide Library)
0 (Peptides)
تواريخ الأحداث: Date Created: 20110928 Date Completed: 20120412 Latest Revision: 20220317
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC3245989
DOI: 10.1093/neuonc/nor141
PMID: 21946118
قاعدة البيانات: MEDLINE
الوصف
تدمد:1523-5866
DOI:10.1093/neuonc/nor141