Abstract 4338: The follicle-stimulating hormone receptor: A new tumor vascular endothelial target for imaging and therapy in animal models

Abstract

Abstract The follicle stimulating hormone receptor (FSHR) is a cell surface receptor expressed in the adult human organism only in the ovary and testis by granulosa and Sertoli cells, respectively, and to a lower extent by the endothelial cells (ECs) of gonadal blood vessels. Here we report that FSHR is also expressed by the vascular ECs of some types of tumors in mice and it is accessible to ligands delivered intravenously. We analyzed by immunohistochemistry tumors generated in nude mice by injecting human cell lines and also tumors that occur in transgenic mice that express oncogenes. Consistent FSHR expression by the ECs has been found in mouse tumors generated by the human prostate cell line LNCaP, and in tumors that appear in the polyoma virus middle T oncogene mouse model of breast carcinogenesis. The most robust expression of FSHR by ECs was found in the xenograft tumors generated by injecting the cell line A431 derived from a human epidermoid carcinoma. In a few other tumor types the expression of FSHR by the tumor vascular ECs was less frequent or absent. We investigated also by immunohistochemistry in mouse models the relation between expression by ECs of FSHR and VEGFR2/KDR, a well established marker of angiogenesis. The possibility of using FSHR expressed by tumor ECs for targeted imaging and therapy was explored in mice that carried xenograft LNCaP tumors. We coupled anti-FSHR extracellular domain antibodies to gold particles and perfused the mice with the complexes for 20 minutes. The vasculature was subsequently washed by perfusion and the tissues have been fixed and processed for electron microscopy. Numerous FSHR-gold particles bound to the surface of the tumor endothelium were visible, while there were no particles attached to the ECs in the normal tissues (prostate and lung). The reported data are relevant in the context of our recent finding that FSHR is expressed by ECs in a wide range of human tumors (manuscript submitted). The mentioned animal models can be used to evaluate the potential of FSHR for targeted tumor imaging and therapy based on FSHR ligands delivered intravenously. The mouse models could be also useful for investigating the mechanism of induction of FSHR expression in the tumor ECs and its potential role in tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4338.