GRP78-targeted nanotherapy against castrate-resistant prostate cancer cells expressing membrane GRP78.

Glucose-regulated protein 78, GRP78, is a chaperone protein mainly located in the endoplasmic reticulum (ER) of normal cells. In stress conditions, GRP78 is overexpressed and in different cancer cell types, it is expressed at the cell surface, whereas it stays intracellular in non-cancerous cells. T...

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Publicado en:Targeted Oncology Vol. 8; no. 4; pp. 225 - 231
Autores principales: Delie, Florence, Petignat, Patrick, Cohen, Marie
Formato: Journal Article
Publicado: Springer Nature Dec2013
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2013
      vid: 8
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11523-012-0234-9
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        atl: GRP78-targeted nanotherapy against castrate-resistant prostate cancer cells expressing membrane GRP78.
      aug:
        au:
          Delie, Florence
          Petignat, Patrick
          Cohen, Marie
        affil: School of Pharmaceutical Sciences, University of Geneva, Quai Ernest Ansermet 30, 1211, Geneva 4, Switzerland.
      sug:
        subj:
          Proteins Metabolism
          Nanoparticles
          Paclitaxel Administration and Dosage
          Prostatic Neoplasms Drug Therapy
          Antibodies Administration and Dosage
          Antibodies Immunology
          Apoptosis Drug Effects
          Cell Line, Tumor
          Proteins Immunology
          Male
          Drug Therapy Methods
          Oligopeptides Immunology
          Prostatic Neoplasms Metabolism
          Prostatic Neoplasms Pathology
          Peptides
          Signal Transduction
          Male
      ab: Glucose-regulated protein 78, GRP78, is a chaperone protein mainly located in the endoplasmic reticulum (ER) of normal cells. In stress conditions, GRP78 is overexpressed and in different cancer cell types, it is expressed at the cell surface, whereas it stays intracellular in non-cancerous cells. Therefore, it appears as a strategic target to recognize malignant cells. Prostate cancer is one of the most diagnosed cancers in men. The development of castrate resistant tumors and the resistance to chemotherapy frequently occur. The carboxy-terminal ER retention domain is defined by the KDEL amino acid sequence. We developed anti-KDEL functionalized polymeric nanoparticles (NPs) loaded with paclitaxel (Tx) to specifically target prostate cancer cells expressing GRP78. The sensitivity to Tx in different formulations was compared in three prostate cell lines: PNT1B, a normal cell line, PC3, a cancer cell line faintly expressing GRP78 at its surface, and DU145, a cancer cell line expressing GRP78 at its cell surface. Our results show that the targeted formulation significantly increases Tx sensitivity of cell line expressing GRP78 at its surface compared to other treatments suggesting the added value of GRP78 targeted therapy for castrate resistant tumor which expresses GRP78 at its cell surface.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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