by ecancer reporter Clare Sansom
The follicle-stimulating hormone (FSH), found in all mammals including humans, is crucially involved in growth, pubertal maturation and reproduction. It is secreted mainly in the anterior pituitary gland but functions in the reproductive organs. It acts by binding to and stimulating a G-protein coupled receptor, the follicle-stimulating hormone receptor (FSH receptor). In healthy humans the FSH receptor is expressed only in these organs: mainly in the granulosa cells of the ovary in females, and in the Sertoli cells of the testis in males. Previous work has indicated that this hormone is expressed on the surface of blood vessels associated with prostate tumours. Now, however, researchers from Mount Sinai School of Medicine in New York, USA, with co-workers from Paris and Poitiers, France, have discovered it to also be expressed in endothelial cells in a wide range of human tumours and in a mouse xenograft model.
The researchers obtained tumour specimens from 1336 patients who had not had hormone therapy prior to surgery. These specimens represented a wide range of primary organs and tumour grades, including early T1 tumours. They used immuno-histochemical and immunoblotting techniques with four monoclonal antibodies, each recognising a different epitope of the FSH receptor, to probe the presence of this receptor in the tumour tissue and its associated blood vessels.
An initial analysis, confined to prostate tumours, showed conclusively using three different monoclonal antibodies that the endothelial cells of blood vessels at the periphery of these tumours stained positive for the FSH receptor. FSH receptor positive cells were also seen in blood vessels associated with benign prostate hyperplasia, but with a different anatomical distribution from those in tumours, indicating that imaging the FSH receptor might be useful as a test to distinguish these two conditions.
Similar studies were then performed with tumours from a variety of other organs. Without exception, the FSH receptor was shown to be expressed in the endothelium of blood vessels associated with all tumours tested. In contrast, endothelial cells from blood vessels associated with non-cancerous tissue from the same organs stained negative for the receptor, with the exception of some very faint signals seen in ovarian and testicular blood vessels. No expression was also observed in tissue from patients with chronic inflammatory conditions. In all cases, FSH receptor expression was seen to be localised in “shells” of about 10mm depth at the tumour periphery, with no expression deeper inside the tumours. The same localisation pattern was seen using immuno-electron microscopy in a human tumour xenograft mouse model.
The researchers suggest that the universal nature of FSH receptor expression at the periphery of human solid tumours makes it a valuable target for both imaging and therapy. The precise localisation of the signal might be useful in defining tumour volumes for targeted radiotherapy or surgery. Furthermore, as expression was seen to be higher than that usually observed in the normal testes and ovaries, it may be possible to design FSH-receptor targeted chemotherapy at dose levels that would not affect these vital tissues.
Radu, A., Pichon, C., Camparo, P., Antoine, M., Allory, Y., Couvelard, A., Fromont, G., Hai, M.T. and Ghinea, N. (2010). Expression of Follicle-Stimulating Hormone
Receptor in Tumor Blood Vessels. N Engl J Med 363:1621-30.