Circulating GRP78 antibodies from ovarian cancer patients: a promising tool for cancer cell targeting drug delivery system?
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Kylie Van Hoesen1, Sonia Meynier1, Pascale Ribaux1, Patrick Petignat1, Florence Delie2 and Marie Cohen1
1Department of Gynecology Obstetrics, University of Geneva, 1205 Geneva, Switzerland
2School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1205 Geneva, Switzerland
Marie Cohen, email: [email protected]
Keywords: membrane GRP78; anti-GRP78 autoantibodies; targeted therapy; ovarian cancer; chorioallantoic membrane
Received: May 04, 2017 Accepted: September 04, 2017 Published: November 11, 2017
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.
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