Lactate for carcinogenesis may explain ‘Warburg Effect’

Otto Warburg discovered that cancer cells were low in oxygen due to a change in cellular respiration — from using oxygen to using fermentation of sugar.

“Cancer, above all other diseases, has countless secondary causes. But, even for cancer, there is only one prime cause,” Warburg said. “Summarized in a few words, the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.”

Cancer cells are low in oxygen primarily because they have changed from taking in and utilizing oxygen for respiration to a more primitive form of respiration which utilizes sugar instead of oxygen. It is the cancer process itself which causes most of the lack of oxygen, not the lack of oxygen which causes the cancer process. [1]

Led by Iñigo San-Millán, director of the Sports Performance Department and physiology laboratory at the University of Colorado's Sports Medicine and Performance Center, researchers have examined the role of lactate in angiogenesis (the process by which new blood vessels form inside the tumors), immune escape (the cancer cells' ability to elude the body's immune response), and cell migration, as well as in 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. and self-sufficient metabolism. [2]

“We still do not know the ‘why’ or the ‘purpose’ of the Warburg Effect, its role in cancer growth and carcinogenesis, or how to halt or reverse metabolic dysregulation in cancer cells,” San-Millán said.

The researchers noted despite lactate being the end product of the Warburg Effect, lactate does not just “sit around;” lactate turnover is significant in resting individuals and very high during exercise far exceeding the glucoseA type of sugar; the chief source of energy for living organisms. turnover rate.

“In cancer, it seems plausible to think that many of, or all the highly orchestrated oncogene and tumor suppressor mutations promoting glycolysis, lactate formation and distribution, while at the same time suppressing oxidative disposal of lactate, are all actors in the same play, the subtitle of which is ‘The Warburg Effect,’ ” San-Millán notes. “In other words, we posit that lactagenesis for carcinogenesis is the purpose of the Warburg Effect in cancer cells and tumors.”

• What is lactagenesis?

The research was published in the journal Carcinogenesis. [3]