Vascular Endothelial FSH Receptor, a Target of Interest for Cancer Therapy

Improved molecular understanding of tumor microenvironment has resulted in the identification of various cancer cell targets for diagnostic and therapeutic interventions, including the receptor for the FSH, a glycoprotein hormone responsible for growth, maturation, and function of human reproductive system. The expression and localization of the FSH receptor (FSHR)-protein were associated with the tumor epithelial cells and/or with the peripheral tumor blood vessels. The available evidence indicates that in ovarian cancer, prostate cancer, and breast cancer, the tumor epithelial FSHR promotes proliferation, migration, and invasion of cancer cells. The vascular endothelial FSHR, detected in 11 types of solid tumors and 11 types of sarcomas, is involved in receptor-mediated transendothelial transport of FSH, tumor angiogenesis, and vascular remodeling. In contrast to intratumor vessels, which are abnormal and disorganized, the FSHR-positive blood microvessels are arranged in a hierarchical pattern: arterioles-capillaries-venules. The FSHR-positive blood vessels make connections between the intratumor vessels and the general blood circulation of patients. In this mini-review, I summarize these studies and discuss the rationale for developing a strategy for cancer therapy based on FSHR expressed on the luminal endothelial cell surface of blood vessels located in the peritumoral area rather than endothelial markers expressed in the core of tumors. Because FSHR is a common marker of peritumoral vessels, therapeutic agents coupled to anti-FSHR humanized antibodies should in principle be applicable to a wide range of tumor types.