Study points to lactate as key driver of cancer

A professor with University of California, Berkeley, is on a research team that paints lactate in a more sinister light -- as a key driver in the development and spread of cancer.

George Brooks, a renown researcher of the complex, often misunderstood molecule, spent two years working with Inigo San Millan, director of the sports performance department and physiology laboratory at the University of Colorado (CU) Sports Medicine and Performance Center at CU Boulder, on a paper recently published in the journal Carcinogenesis.

For decades, lactate has been studied largely in the context of exercise, painted as a nagging metabolic byproduct that accumulates in the tissues and blood during workouts, stiffening muscles and hindering performance.

As far back as 1923, German Nobel laureate Otto Warburg observed that cancer cells take in exponentially more sugar, or glucose, than normal cells. They inefficiently convert far less of it into energy, rather converting about 70 percent of it to lactate as a byproduct. The phenomenon, the first sign of a normal cell turning cancerous through abnormal cell metabolism, is known as the "Warburg effect."

With a heightened focus on genetics in recent decades, most researchers moved away from studying cancer metabolism, and the role of lactate became overshadowed, San Millan said.

The new study illuminates the role lactate plays in fueling angiogenesis, or the formation of new blood vessels in tumors; how it interferes with the body's immune response to cancer; and how it creates an acidic microenvironment, or the space outside the cancer cell, supportive of cancer metastases, or spread.

It also theorizes how three major transcription factors, or proteins, involved in most cancers, namely HIF-1,cMYC, and p53, kick-start and perpetuate lactate deregulation in cancer.

The paper draws parallels between what happens in the muscles of an athlete in training, and what happens in a developing cancer.

"During high-intensity exercise, working muscles display many of the same metabolic characteristics as cancer cells," San Millan, a former pro cyclist and physiologist to Tour de France cyclists, was quoted as explaining in a news release from CU Boulder. Muscles take up large amounts of glucose, turning it to energy inside the mitochondria and churning out more lactate than the body can immediately clear.

In a healthy person, Brooks' research has shown, the body then recycles that lactate for beneficial use, turning it into a key source of fuel for the brain, muscles, and organs, preventing it from building up. In cancer, the authors of the paper suggest, that recycling system breaks down.

While people who exercise regularly are at less risk of cancer, in part due to their body's ability to clear lactate more efficiently, San Millan noted, a sedentary lifestyle, combined with excess sugar intake may fuel lactate accumulation and kick-start the metabolic misfiring that can lead to cancer.

source: Xinhua