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Targeted Oncology
Published in: Targeted Oncology 4/2013

01-12-2013 | Original Research

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

Authors: Florence Delie, Patrick Petignat, Marie Cohen

Published in: Targeted Oncology | Issue 4/2013

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Abstract

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.
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Metadata
Title
GRP78-targeted nanotherapy against castrate-resistant prostate cancer cells expressing membrane GRP78
Authors
Florence Delie
Patrick Petignat
Marie Cohen
Publication date
01-12-2013
Publisher
Springer Paris
Published in
Targeted Oncology / Issue 4/2013
Print ISSN: 1776-2596
Electronic ISSN: 1776-260X
DOI
https://doi.org/10.1007/s11523-012-0234-9

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