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.
Now a provocative new paper, published in February in the journal , paints the complex, often misunderstood molecule in a more sinister light鈥攁s a key driver in the development and spread of cancer.
Its authors say the paper could help explain why people who exercise tend to have lower rates of cancer鈥攂ecause their bodies are able to more effectively process the lactate we all produce when we metabolize sugar. It also could lead to new treatments.
鈥淲ith this paper, we open a whole new door for understanding cancer, showing for the first time that lactate is not only present, but mandatory for every step in its development,鈥� said lead author Inigo San Millan, director of the sports performance department and physiology laboratory at the CU Sports Medicine and Performance Center at 兔子先生传媒文化作品.
San Millan, also an assistant professor in the at the CU School of Medicine, spent two years working on the paper with University of California Berkeley professor and renown lactate researcher George Brooks. The team applied lessons learned from dozens of exercise physiology and muscle metabolism studies conducted at 兔子先生传媒文化作品, the CU Anschutz Medical Campus in Aurora, the University of California and elsewhere to try to answer a century-old question: How does a normal cell become a cancer cell and then what happens?
Inigo San Milan uses a new hand-held ultrasound technology for a study involving听pro cyclist Chris Winn. (Photo by Glenn Asakawa/University of Colorado)
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 also inefficiently convert far less of it into ATP, or energy, converting about 70 percent of it to lactate as a byproduct. The phenomenon鈥攖he first sign of a normal cell turning cancerous through abnormal cell metabolism鈥攊s known as the 鈥淲arburg effect.鈥� The paper seeks to explain why it happens.
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. He hopes to help swing the pendulum back.
The paper illuminates the role lactate plays in fueling angiogenesis (the formation of new blood vessels in tumors); how it interferes with the body鈥檚 immune response to cancer; and how it creates an acidic microenvironment (the space outside the cancer cell) supportive of cancer metastases, or spread. The paper also theorizes how three major transcription factors, or proteins, involved in most cancers (HIF-1,cMYC, and p53) kick-start听and perpetuate听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.
鈥淒uring high-intensity exercise, working muscles display many of the same metabolic characteristics as cancer cells,鈥� explains San Millan, a former pro cyclist and physiologist to Tour de France cyclists. 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鈥� research has shown, the body then recycles that lactate for beneficial use鈥攖urning it into a key source of fuel for the brain, muscles听and organs, preventing it from building up.
In cancer, the authors suggest, that recycling system breaks down.
We hope to sound the alarm for the research community that to stop cancer you have to stop lactate. There are many ways to do that.鈥� 鈥擨nigo San Millan
San Millan hypothesizes that while people who exercise regularly are at less risk of cancer鈥攊n part due to their body's ability to clear听lactate more efficiently鈥攁 sedentary lifestyle, combined with excess sugar intake may fuel lactate accumulation and kick-start the metabolic misfiring that can lead to cancer.
The authors hope cancer researchers will use the paper as a starting point for further studies. Already, San Millan is studying breast cancer cell lines, and this summer he will team up with University of Colorado Hospital to study the impact of personalized exercise programs on cancer patients.
Ultimately, he hopes the paper could lead to new exercise and dietary prescriptions for cancer patients, new diagnostic tools that could use deregulated lactate signaling as a marker of a brewing cancer, or new drugs which target MCT Transporters, which are responsible for transporting lactate from cell to cell.
鈥淲e hope to sound the alarm for the research community that to stop cancer you have to stop lactate,鈥� he said. 鈥淭here are many ways to do that.鈥�
