Follicle-stimulating hormone (FSH) receptor is selectively expressed on the surface of the blood vessels in a wide range of tumors and could be a candidate for tumor imaging and therapy, according to a study published in the Oct. 21 issue of the New England Journal of Medicine.
The team consisted of researchers from Mount Sinai School of Medicine in New York City, in collaboration with investigators of the National Institute of Health and Medical Research (INSERM) of Paris, and was led by Nicolae Ghinea, PhD, from INSERM.
Ghinea and colleagues discovered that FSH receptor which is not present on the blood vessels of any normal tissues with the exception of reproductive organs was also found in blood vessel cells in a wide range of tumor types.
"This new tumor marker may be used to improve cancer detection. Tumor imaging agents that bind to the new marker could be injected in the vasculature and would make visible early tumors located anywhere in the body using magnetic resonance imaging, PET or ultrasound imaging," said the study's lead author, Aurelian Radu, PhD, assistant professor of developmental and regenerative biology, Mount Sinai School of Medicine.
Scientists evaluated tissue samples from the tumors of 1,336 people in 11 common cancer types, including prostate, breast, colon, pancreatic, lung, liver and ovarian. They used as detection reagents antibodies that act as homing devices to the FSH receptor. The research team found that the antibodies located the FSH receptor on the cells that form the blood vessel walls in the periphery of tumors, extending both internally and externally in the immediate vicinity of the tumor.
Activation of the FSH receptor is known to contribute to the signaling of vascular endothelial growth factor (VEGF), a protein that stimulates the growth of blood vessels, including those in tumors. Therefore, blocking the action of the FSH receptor may also block signaling of VEGF, according to Radu and colleagues.
The team showed that the endothelial FSH receptors were accessible to intravenously delivered ligands using an in situ animal model: mice. Immunoelectron microscopy in mice with xenograft tumors, after perfusion with anti-FSH-receptor antibodies coupled to colloidal gold, showed that the FSH receptor is exposed on the luminal endothelial surface and can bind and internalize circulating ligands.
“If it becomes possible to exploit FSH-receptor expression for imaging purposes, the location of the FSH receptor signal at the boundary between the tumoral and the normal tissues should make it useful for defining the target volume for radiation therapy or surgery,” noted Radu and colleagues.