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Circulating GRP78 antibodies from ovarian cancer patients: a promising tool for cancer cell targeting drug delivery system?
- Source :
- Oncotarget (2017), Oncotarget
- Publication Year :
- 2017
-
Abstract
- Glucose-regulated protein 78 (GRP78) is a chaperone protein that has a high frequency in tumor cells. Normally it is found in the endoplasmic reticulum to assist in protein folding, but under cellular stress, GRP78 influences proliferative signaling pathways at the cell surface. The increased expression elicits autoantibody production, providing a biomarker of ovarian cancer, as well as other types of cancer. This study aims to determine the epitope recognition of GRP78 autoantibodies isolated from serum of ovarian cancer patients and use the identified antibodies to design new drug delivery systems to specifically target cancer cells. We first confirmed that the membrane GRP78 levels are increased in ovarian cancer cells and positively correlate with proliferation. However, the level of circulating GRP78 autoantibodies did not correlate with membrane GRP78 expression in ovarian cancer cells and was lower, although not significantly, compared to control patients. We then determined the epitope recognition of GRP78 autoantibodies and showed that treatment with paclitaxel-loaded nanoparticles coated with anti-GRP78 antibodies significantly decreased tumor development in chick embryo culture of ovarian cancer cell tumors compared to paclitaxel treatment alone. This evidence suggests that nanoparticle drug delivery systems coupled with antibodies against GRP78 has potential as a powerful therapy against ovarian cancer.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
medicine.medical_treatment
Epitope
Targeted therapy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
Medicine
ddc:615
ddc:618
biology
business.industry
membrane GRP78
chorioallantoic membrane
Autoantibody
Cancer
targeted therapy
medicine.disease
anti-GRP78 autoantibodies
ovarian cancer
030104 developmental biology
Paclitaxel
chemistry
030220 oncology & carcinogenesis
Cancer cell
Cancer research
biology.protein
Antibody
business
Ovarian cancer
Research Paper
Subjects
Details
- Language :
- French
- ISSN :
- 19492553
- Database :
- OpenAIRE
- Journal :
- Oncotarget (2017), Oncotarget
- Accession number :
- edsair.doi.dedup.....95908e2fe148dee8e5325fa1f1de2e2e