Fatty Diet Makes Cancer Aggressive

THE GIST:

• Cancer cells use fat molecules as signalling tools.
• The cancer cells signal each other to grow larger and more dangerous.
• The discovery was made in the lab and in mice.

Obesity, or a diet high in fats, can kick-start a benign tumor into life-threatening cancer, according to new research published in the journal Cell.

In the study, scientists from Scripps Research Institute found a new enzyme, known as MAGL, that human cancer cells use to turn fat into a signaling molecule, essentially talking itself into growing larger and more dangerous.

The research means that patients recently diagnosed with cancer could be prescribed a diet low in fat to slow the growth of the cancer, also helps explain the link between cancer and obesity.

"The implication of this study are that a person with an aggressive cancer, if they are eating a diet high in fat or are obese, could exacerbate the cancer's growth," said Daniel Nomura, a co-author of the study.

Scientists have known that obesity is linked with higher rates of pancreatic, breast, kidney, esophageal, and other cancers cancers for years. Why obesity and cancer are linked is still largely a mystery, however. Various factors, such as increased acid reflux to insulin levels, explain some of the data for specific cancers, but no general, all-encompassing model linking the two has been found.

The new study doesn't completely explain the link between cancer and obesity, says Nomura, but it gives yet another explanation for the link.

The body uses fat to store excess energy that it cannot use right away. When a person works out, the body taps into those stores of fat to provide energy for, say, running legs or weight-lifting arms.

The human breast, ovarian and colon cancer cells that the Scripps scientists implanted into mice didn't seem to use fat as an energy source though. Instead, they used the fat molecules to talk with themselves. The scientists discovered that an enzyme known as monoacylglycerol lipase, or MAGL for short, was turning the fat into a signaling molecule. In essence, the cancer cells found a way to talk to themselves, constantly encouraging themselves to grow ever bigger and more dangerous.

Where the fat came from didn't matter. If the mice were obese the fat came from their own tissues. If the mice were normal sized, but eating a high-fat diet, then the cancer used the fat from the food to encourage themselves to grow ever bigger.

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When the scientists reduced the amount of MAGL in the mice the tumor didn't grow nearly as fast. After about one month low MAGL mice on a normal diet had tumors nearly 75 percent smaller compared with mice on a high-fat diet or obese mice. Mice with low levels of MAGL but who ate a high-fat diet however, saw their tumors grow to almost the same size as the control mice with high levels of MAGL.

The cancer cells the researchers implanted into the mice were bred to be aggressive. The scientists created the aggressive cancer cells by growing the cancer in petri dishes and selecting the tumors that grew the most, and implanted those cell into the mice. Introducing large amounts of fat caused already aggressive cancer cells to grow faster, but it didn't create the aggressive cancer.

That wasn't true for the cancer cells in the petri dish. Merely introducing large amounts of fat onto the petri dishes turned a slow growing cancer into a fast, aggressive cancer.

Nomura is careful to point out that these experiments were done in mice and in petri dishes under controlled conditions. Other scientists agree that doctors and patients shouldn't make any decisions on how to treat an actual cancer based on this study, or at least until other studies have come out.

Nevertheless, the research fills an important gap in our knowledge about cancer and how it relates to obesity, says Brendan Manning, a scientist at Harvard University who wrote an accompanying article in Cell but was not involved with the research.

"The research on obesity and cancer has so far mostly focused on cancer and deaths," said Manning. "Very little study has been done about cancer progression however."

Manning says the new research could eventually lead to new anticancer drugs that slow the progression of tumors and give patients extra months or maybe even years. The first drug candidate is the one the Scripps scientists used to inhibit MAGL during their experiments. Before that could be brought to market however, years of clinical trials and FDA approval will be required.

"I don't think the study warrants going on a low-fat diet if you are diagnosed with cancer," said Manning. "But it does warrant future clinical study."