Scientists identify key component in lethal lung cancer complication

A protein previously thought not to exist in adult human lungs not only is present in normal and cancerous lung tissue, scientists have found, but it also has a major role in the development of a lethal complication of some lung cancers.

The protein, called the calcium-sensing receptor, sits on the surface of lung cancer cells that make up tumors known as squamous-cell carcinomas, according to new research.

As these tumors grow, the receptor releases a hormone that sets off a biological cycle that leads to the erosion of bone throughout the body. When the bone breaks down, calcium is released. The excess calcium that can’t be filtered by kidneys cycles back to the receptors, which release more of the damaging hormone. That same hormone promotes the growth and spread of cancer.

The result is a syndrome called hypercalcemia, a debilitating disorder that signals lung cancer patients will survive only about three more months and eventually leads to acute multi-organ system failure.

Knowing the receptor’s role in squamous-cell lung cancers will help guide future research on new treatment options for both the cancer and hypercalcemia, said Gwendolen Lorch, assistant professor of veterinary clinical sciences at Ohio State University and lead author of the study.

“The calcium-sensing receptor clearly has a huge role in hypercalcemia. Though it’s too soon to say it could be a target for treatment, we won’t ever be able to find the right target if we don’t know how hypercalcemia develops in the first place,” Lorch said.

The researchers also found that lung cancer patients who have a specific type of inherited genetic mutation are at risk of developing hypercalcemia earlier than others. This finding is likely to have clinical implications in the future, as sequencing of the human genome becomes more affordable and available as part of standard medical care, Lorch said.

The research is published in a recent issue of the journal Neoplasia.

Before this study, previous research had established that the calcium-sensing receptor is important to lung development because mice lacking the receptor showed stunted lung growth. But its presence had never been documented in adult human lungs.

Researchers also knew that hypercalcemia was associated with unregulated release of a specific hormone, and that it developed in patients with cancers based in the epithelia, or tissue that makes up the lining of organs, blood vessels and body cavities. Squamous-cell carcinoma of the lung is one of these types of cancers.

Despite all that was known, however, the connection between the receptor and hypercalcemia had never been established in lung cancer. Studies suggest that anywhere from a fourth to two-thirds of lung cancer patients will develop the deadly syndrome.

Hypercalcemia symptoms include nausea and vomiting, loss of appetite, heart arrhythmia, high blood pressure and acute kidney failure. Most patients suffer dementia, become irritable and have sleep problems, and eventually have seizures, slip into a coma and die.