Targeting RAGE Expression in Human Ovarian Cancer

Tekabe Y, Li Q, Rodriguez K, Johnson J, Khaw BA, Kokoshka J, Ray R, Rai V and Johnson L

Department of Medicine, Columbia University Medical Center, New York, USA
Department of Pharmaceutical Sciences, Northeastern University, USA
Department of Technology Ventures, Columbia University, New York, USA
Institute of Life Sciences, Department of Biotechnology, Bhubaneswar, India

^*Correspondance to: Yared Tekabe 

 PDF  Full Text Case Report | Open Access

Abstract:

Receptor for Advanced Glycation Endproducts (RAGE) is expressed in ovarian tissue and associated with ovarian carcinoma. With a radiolabeled anti-RAGE antibody, we proposed to show extent of RAGE expression in animal model and effect of blocking RAGE on ovarian cancer cell growth.
Methods: We measured inhibition of p-Akt and p-stat3 in SKOV-3 human ovarian carcinoma cell line and measured cell growth suppression in culture. For imaging, female nude mice (n = 15) at 6 wks of age were injected with luciferase expressing human ovarian cancer cells into the right flank. Four-five weeks later, animals were injected with luciferin and imaged on optical imager followed by injection with 111In-anti-RAGE F(ab’)2 (n = 7) or 111In-control IgG F(ab’)2 and 48 h later, were imaged on micro-SPECT/CT. Focal tracer uptake on scans was quantified, the tumors removed, radioactivity counted, and sectioned for histological and immunohistochemical examination.
Results: RAGE antibody pretreatment inhibited p-stat3 and p-AKT expression in SKOV-3 cells and there was a dose related reduction in cell growth in culture. There was good co-localization of the luciferase producing tumor on the optical scan and tumor location at necropsy with the focal uptake of the 111In-anti-RAGE F(ab’)2. Quantitative tracer uptake in the tumor from scans showed that uptake of 111In-anti-RAGE F(ab’)2 as %ID was 2.4 fold higher than 111In-control F(ab’)2 (P = 0.01) confirmed by gamma well counting. Dual immunofluorescent staining for RAGE and PAX8 in tumors showed high expression of RAGE and co-localization with PAX8 positive stained cells.
Conclusion: RAGE expression in ovarian tumors in live animals can be imaged and quantified. An anti-RAGE F(ab’)2 used for imaging shows blocking properties and suppresses ovarian cancer cell growth.

Keywords:

Ovarian cancer; RAGE; SPECT/CT Imaging

Cite the Article:

Tekabe Y, Li Q, Rodriguez K, Johnson J, Khaw BA, Kokoshka J, et al. Targeting RAGE Expression in Human Ovarian Cancer. Clin Oncol. 2016; 1: 1055.