Scientists Reveal How Lactic Acid Affects Cancer's Pathogenesis
Have you ever had the experience that after an accidental strenuous exercise, the muscles in the area of exercise were sore and painful, the arms were difficult to lift, and even the legs were robotically stiff to the point of "walking"?Many people believe that the "criminal" behind this may be lactic acid.
After strenuous exercise, the buildup of lactic acid produced by the muscles can cause symptoms of muscle soreness.But when lactic acid moves from the stadium to the cancer research arena, its role is far more complex than we think—lactic acid may be surprisingly linked to the malignant nature of cancer associated with it.
Recently, Chinese scientists found in the study published in Nature-Metabolism that elevated circulating lactic acid levels in the human body or produced cancerous substances make patients thin, thus reducing cancer treatment tolerance and survival.
How did they "catch" this killer?China Science Journal interviewed Xiao Ruiping, dean of Peking University's School of Future Technology, and Hu Xinli, a researcher.
Find the "true culprit"
Some cancer patients will be extremely thin, the shape of the bone, which is related to the common complications of cancer "bad disease quality".
Bad substances, also known as bad fluids, are systemic metabolic diseases that occur more frequently in patients with serious diseases such as cancer.Clinical statistics show that malignant diseases affect about 50 to 80 percent of cancer patients, accounting for about 20 percent of cancer-related deaths.
"Vicious diseases not only cause patients to lose weight, but also cause malnutrition, exhaustion of systemic energy, and weakened immune system function.Hu Xinli, the author of the paper, said that this will increase the risk of infection after surgery, more susceptible to drug side effects, and even seriously affect the normal functioning of organs.
However, the mechanism of the occurrence of malignant diseases is not clear, and its clinical treatment lacks effective means.
Only one drug, Anamolin, is available in Japan, which can improve patients' appetite in the short term, but has not been approved by the European Union and the U.S. Food and Drug Administration because it cannot substantially improve muscle strength and survival.
How does evil happen?With this problem, the research team embarked on a five-year "crime arrest" road.
"Cancer cells take in large amounts of glucose for rapid proliferation and produce large amounts of lactic acid, the 'Waberg effect'.Xiao Ruiping explained to China Science Journal that from this effect, they carried out unbiased screening of metabolites in the blood of malignant patients and mice, and after a long period of tracking, finally let the "true culprit" - lactic acid surface.
To make the conclusion more convincing, the team constructed models of mice with malignant pathologies, and found that mice implanted with cancer showed significant weight loss, reduced white adipose tissue and skeletal muscle mass.
Further experiments showed that continuous administration of lactic acid to mice kept the lactic acid in the mice's blood at the level it was at when the malignancy was present, even if the mice did not have tumors.This suggests that lactic acid itself can indeed induce malignant substances.
Treatment of new ways out
How Does Lactic Acid Cause Bad Diseases?To eliminate the impact of this "murderer" on cancer patients, it is necessary to understand its "crime" path.
Combined with previous research, the team found that the receptor for lactic acid, GPR81, a protein molecule that senses lactic acid on cells, plays a key role.
They found that lactic acid stimulates browning and fat breakdown of adipose tissue by binding to the receptor GPR81 expressed in white adipose tissue, which leads to muscle atrophy and weight loss."We found that mice without the lactic acid receptor GPR81 did not experience weight loss, fat loss and muscle atrophy after developing tumors." said Shorepin.
"Vicious diseases have a serious impact on the quality of life and survival of patients.Hu Xinli said that the study found that blocking the lactic acid receptor GPR81 can limit the body's energy depletion caused by tumors, which undoubtedly brings hope to more patients with malignant diseases.
However, Hu Xinli said that blocking the GPR81 receptor, which helps lactic acid "murder", does not mean "completely eliminating it".The receptor is expressed not only in adipose tissue, but also in the nervous system and various glands, and has multiple important physiological functions.Even "direct removal" only in adipose tissue can cause metabolic disorders.For this reason, controlling the overactivated lactic acid/GPR81 signal is a better way to do so through targeted therapy.
The study also found that lactic acid receptor GPR81 plays an important role in promoting tumor growth and metastasis, so inhibitors targeting this receptor may kill two birds with one stone – playing a dual role in fighting cancer and improving malignant diseases.
"Because patients with malignant diseases are usually weak, sample acquisition is difficult, especially thanks to the patients who provided valuable samples for our study, and their dedication provides important support for our study and hope for more malignant patients.""What is it?" said Hu Xinli.
So, can changes in lactic acid levels be used for weight regulation in healthy people?
Hu Xinli said that the effect of changes in lactic acid levels on body metabolism under normal physiological conditions is also one of the important areas of the team's research, but whether exercise relies on lactic acid/GPR81 for weight loss.
Clinical transformation requires in-depth study
"This broadens our understanding of lactic acid signaling, adipose tissue function, and cancerous pathologies."Professor Marcus D. Will Cornell Medical School, Cornell University. Goncalves said in a news opinion article published at the same time that based on this discovery, it will help develop new therapies and new methods for targeting GPR81.
Although lactic acid receptor GPR81 is a potential target for clinical conversion, Xiao Ruiping, a longtime translationalist, says translating basic research into clinical applications is a complex and challenging process, as is the case with this study.
For example, in terms of technological transformation, the study found that although therapeutic targets were found, "target" is not enough, and available drugs need to be developed to study and improve the safety, effectiveness, and production process."This process requires the integration of expertise in different fields, consumes a lot of resources, and requires a good ecosystem of 'industry-academic-research-medical-government-use' to achieve this."" she said.
Xiao Ruiping said that although China's basic research results are fruitful, whether the number of published papers or the number of patents granted has increased significantly, the current shortage of capital and clinical research personnel will still hinder the transformation of these results.In the future, with the maturity of the transformation mechanism and the strengthening of national policy support, it will help promote the development of transformation medicine.
Next, Hu said, the research team will further explore the significance of physiological changes in lactic acid levels on the metabolism of the body, and the direct relationship between skeletal muscle atrophy and lactic acid in malignant substances.They will also develop GPR81 antagonists to fill the current gap in targeting GPR81 inhibitors.