An insulin-like hormone speeds the destruction of bone caused by malignant tumors, a team of clinical pathologists has found. "The study answers a fundamental question," says Jonathan Waxman, an oncologist at Imperial College London. If confirmed, the results could eventually point to drugs for slowing or stopping the damage to bones caused by cancers.
Known as relaxin, the hormone had already been tied to cancer. Previous studies had linked high levels of relaxin to aggressive endometrial and prostate cancer and to those cancers that spread to the bones, such as breast, thyroid, and myeloma. But whether relaxin produced by cancerous tumors could boost the destruction of bone tissue remained unclear.
Indirect evidence suggested that it might, say Alberto Ferlin and Carlo Foresta, clinical pathologists at the University of Padua in Italy and co-authors of the new study. Relaxin belongs to the same class of hormones as the one produced in the testes called INSL3. In earlier work with cultured mouse and human cells, Ferlin and colleagues had shown that, under certain condition, INSL3 interacts with cells called osteoblasts that build up bone tissue. When the testes do not produce enough INSL3, bone mass drops and osteoporosis occurs. "We thought relaxin could trigger a similar effect," says Ferlin. "We were right."
The researchers proved that by studying the effects of relaxin on cultured human bone cells. They found that the hormone stimulates cells called osteoclasts, which normally balance the activity of osteoblasts by removing bone excess tissue through a mechanism called resorption. By binding with a receptor molecule called RXFP1 on the osteoclasts' surface, relaxin triggered runaway resorption, causing the osteoclasts to consume too much bone tissue and release a huge quantity of calcium. In the body, such a flood of calcium into the blood causes hypercalcemia, another severe impairment usually associated with the presence of bone metastases. The researchers also found that relaxin promotes growth, differentiation, and invasiveness of various tumors, especially those that give bone metastases.
When the researchers added an anti-relaxin antibody to the cell cultures, the antibody prevented relaxin from binding with receptors and from triggering bone damage. That finding, which they report in the 2 February issue of Bone, suggests that a drug based on this antibody or one that inhibits the relaxin receptor could slow down bone damage while also preventing hypercalcemia, Foresta says.
"It seems almost too good to be true," says Waxman, who says the findings could be "the point of embarking on a journey" toward treatments that will stop the spread of bone cancer. Finding such a drug will not necessarily be a short trip, though. As far as targeting the RXFP1 receptor, Ferlin and Foresta say there are already peptides available for this purpose. However, they also point out that a new drug designed to target the receptor would be completely new, so side effects are unknown.