Protein implicated in many cancers
Receptor for hormone may be good drug target
By Nathan Seppa
A protein involved in hormone signaling is also produced by blood vessel cells in tumors, a new study finds. The protein showed up in 11 kinds of tumors examined by a French-U.S. research team but was notably absent in most healthy tissues.
The discovery suggests that the protein helps cancer gain a foothold by recruiting blood vessels to nourish the tumor, researchers report in the Oct. 21 New England Journal of Medicine.
“This is strong work with potential for significant clinical impact,” says Edgar Ben-Josef, a radiation oncologist at the University of Michigan in Ann Arbor who was not part of the new study. “This receptor may be a valuable target for suppression.”
Earlier work had linked the protein, called a follicle stimulating hormone receptor, to prostate cancer. In the new study researchers detected the receptor in every one of 773 prostate tumor samples they tested, noting that the receptor turned up in blood vessel cells on the tumors. The FSH receptor didn’t show up at all in healthy prostate tissues from these patients.
The researchers also found this pattern when examining 10 other types of tumors obtained from 563 other patients.
“The fact that it is not a phenomenon confined to prostate cancer only makes this a much more interesting finding,” Ben-Josef says. Activating the receptor probably “confers a worse prognosis,” he says.
The FSH receptor is a protein displayed by cells that latches onto the FSH protein, a hormone that plays several roles in the reproductive system. This binding also might play a role in angiogenesis, the formation of new blood vessels.
The FSH receptor normally shows up in ovaries and testes, and did so in these tests. It also appeared in samples of placental tissue.
While new vessel growth is fine in the placenta — helping the fetus gain nutrition from the mother’s body and grow rapidly — such angiogenesis has a dark side: Tumors fuel their own growth by triggering angiogenesis to obtain blood and nutrients.
“The driving force in tumor growth is the proliferation of the cancer cells, which in turn induces angiogenesis,” says study coauthor Nicolae Ghinea, a cell biologist at the University of Paris-East and INSERM, the French National Institute of Health and Medical Research in Créteil.
The researchers also found that cells with activated FSH receptors tended to cluster at the edges of a tumor. This location, Ghinea says, “is consistent with the view that the tumor cells at the invasive front attract surrounding blood vessels toward the tumor.”
Ghinea and his colleagues are now trying to confirm in animal studies that the FSH receptor really does contribute to tumor growth. The researchers also want to determine whether compounds that inhibit the receptor or the FSH protein itself might constitute new anticancer drugs.
