SPNS2 identified as possible key to metastasis

Sphingolipid Transporter 2 (SPNS2) is a protein-coding gene. A team of researchers at Sanger Institute in Cambridge report that it also led to a three-quarters reduction in tumors spreading to the lungs. [1]

“We've learned some interesting new biology that we might be able to use — it's told us this gene is involved in tumor growth,” said Dr. David Adams, a member of the research team whose findings were published in Nature.

The SPNS2 gene was known to affect the immune system but was not implicated in tumor spread. It codes for a protein that transports a lipid, S1P, which signals to the immune system. Without this transporter protein, the signaling doesn't work properly and results in changes in the proportion of different immune cells in the body.

Dr. Anneliese Speak from the Sanger Institute noted: “This work supports the emerging area of immunotherapy, where the bodies' own immune system is harnessed to fight cancer. Drugs could be designed to bind to the S1P transporter, preventing it from working and causing advantageous changes to the immune system.

“Investigation of further targets in the SPNS2 pathway or other targets identified in this study could help develop potential therapies.”

The spread of tumors — metastasisThe spread of cancer cells from the place where they first formed to another part of the body. In metastasis, cancer cells break away from the original (primary) tumor, travel through the blood or lymph system, and form a new tumor in other organs or tissues of the body. The new, metastatic tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the lung, the cancer cells in the lung are breast cancer cells, not lung cancer cells. — to other sites in the body is the leading cause of death for cancer patients. Up to 90 percent of cancer deaths are due to metastasis, however, the process that regulates the spread of tumors is not understood.

Removal of the SPNS2 gene caused the largest change, reducing the spread of tumors to the lungs by approximately four times. Researchers then looked at the effect of this gene on the spread of other cancers — colon, lung, and breast — and showed that taking out SPNS2 also reduced the metastasis of these cancers.

“Loss of the SPNS2 gene causes the greatest reduction in the formation of tumor colonies and represents a novel therapeutic target,” Dr. Adams said. “We found that mice lacking SPNS2 have a different ratio of immune system cells than normal, which seems to prime the immune system to remove cancer. Drugs that target this could help reduce or prevent the spread of tumors through the body.”

Immunotherapy has been part of the medical lexicon since the 1890s and has entered a renaissance phase. Fifteen FDA-approved immunotherapy agents have been approved since 1986. Currently approved immunotherapy agents target more than 10 different cancer types.

There are more than 600 ongoing immunotherapy clinical trials for cancers such as breast, colon, head and neck, and kidney.

“For the longest time, people did not believe this was possible,” said Lawrence Fong, MD, associate professor of medicine at the University of California-San Francisco and one of the university’s lead investigators in the expanding use of immunotherapy.

“Now we can treat cancer by treating the patient instead of the disease,” Dr. Fong said. “That’s the biggest change. We can treat cancer without delivering chemotherapy or radiation to kill the cancer or performing surgery to get rid of the tumor.”