دورية أكاديمية
Molecular targeting of intracellular compartments specifically in cancer cells.
| العنوان: | Molecular targeting of intracellular compartments specifically in cancer cells. |
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| المؤلفون: | Pandya H; Departments of Neurosurgery, Radiation Oncology, and Cancer Biology, The Brain Tumor Center of Excellence, Wake Forest University, School of Medicine, Winston-Salem, NC, USA., Gibo DM, Debinski W |
| المصدر: | Genes & cancer [Genes Cancer] 2010 May; Vol. 1 (5), pp. 421-33. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals LLC Country of Publication: United States NLM ID: 101516546 Publication Model: Print Cited Medium: Internet ISSN: 1947-6027 (Electronic) Linking ISSN: 19476019 NLM ISO Abbreviation: Genes Cancer Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Publication: 2014- : Albany, NY : Impact Journals LLC Original Publication: Thousand Oaks, CA : Sage Publications |
| مستخلص: | We have implemented a strategy in which a genetically engineered, single-chain protein specifically recognizes cancer cells and is trafficked to a targeted subcellular compartment, such as the nucleus. The recombinant protein termed IL-13.E13K-D2-NLS has a triple functional property: (1) it binds a cancer-associated receptor, interleukin 13 receptor alpha 2 (IL-13Rα2), using modified IL-13 ligand, IL-13.E13K; (2) it exports its C-terminal portion out of the endosomal compartment using Pseudomonas aeruginosa exotoxin A (PE) translocation domain (D2); and (3) it travels to and accumulates in the nucleus guided by the nuclear localization signal (NLS). Here, we have demonstrated that this protein is transported into the brain tumor cells' nucleus, using 3 different methods of protein conjugation to dyes for the purpose of direct visualization of the protein's intracellular trafficking. IL-13.E13K-D2-NLS, and not the controls such as IL-13.E13K-D2, IL-13.E13K-NLS, or IL-13.E13K, accumulated in nuclei very efficiently, which increased with the time the cells were exposed to the protein. Also, IL-13.E13K-D2-NLS did not exhibit nuclear transport in cells with low expression levels of IL-13Rα2. Thus, it is possible to recognize cancer cells through their specific receptors and deliver a conjugated protein that travels specifically to the nucleus. Hence, our molecular targeting strategy succeeded in generating a single-chain proteinaceous agent capable of delivering drugs/labels needed to be localized to the cells' nuclei or potentially any other subcellular compartment, for their optimal efficacy or ability to exert their specific action. |
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| معلومات مُعتمدة: | R01 CA074145 United States CA NCI NIH HHS; R01 CA074145-13 United States CA NCI NIH HHS; R01 CA074145-14 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: cancer; glioblastoma multiforme; molecular targeting; receptors; subcellular compartments; trafficking |
| تواريخ الأحداث: | Date Created: 20100827 Date Completed: 20111110 Latest Revision: 20211020 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC2926990 |
| DOI: | 10.1177/1947601910375274 |
| PMID: | 20740056 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1947-6027 |
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| DOI: | 10.1177/1947601910375274 |