The basic development process of cancer cells

Nearly 80 years ago, scientist Otto Warburg observed that cancer cells exhibited different metabolic processes than normal adult cells. Decades later, this observation was used by clinicians to better visualize tumors thanks to PET (positron emission technology) positron imaging technology. But it is currently unknown how tumor cells achieve this metabolic process and whether this process is important for tumor growth.

Currently, two articles in the March 13 issue of Nature help answer these questions. Conducted by scientists at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, this work finds metabolic processes - known as Warburg effects , which are necessary for thriving tumor mass, and also identified M2 form of pyruvate kinase (PKM2), an enzyme involved in sugar metabolism , an important mechanism behind this process. This discovery may provide a new goal for future cancer treatments.

According to lead author Dr. Lewis Cantley, Director of Cancer Center at BIDMC and Lecturer in Systems Biology at Harvard Medical School 'By this project we have answered the basic question regarding ability rapid growth and proliferation of tumor cells. '

Metabolic coordination in cells grows so rapidly, such as tumors or fetal tissues, differs from coordination in normal adult cells.'Through the Warburg effect, cancer cells produce energy by absorbing glucose at a faster rate than other cells while at the same time they use a smaller rate than glucose sugar in too much. energy production process. '

Otto Warburg scientist (Photo: Nobelprize.org)

This allows cancer cells to be as capable as embryonic cells, growing at a very fast rate.'This unique energy metabolism property of cancer cells has led to the success of PET imaging as a means of detecting cancer; because the radioactive glucose that is injected into the patient before the scan is usually consumed favorably by glucose-hungry tumor cells, and the high glucose consumption areas are clearly shown on PET screen. '

Using a screen of blood protein analysis to identify new phosphotyrosine combinations of proteins, Cantley and colleagues first identified PKM2 as being able to bind to phosphotyrosine-containing chains.'We can observe that, contrary to the forms of pyruvate kinase in most normal adult tissues, only PKM2 found in embryonic cells interacts with pyruvate kinase . This finding is particularly interesting because previous reports show that this M2 type is pyruvate kinase form consumed by all cancer cells. '

To fully understand the significance of this discovery, Cantley and his colleagues will then conduct experiments to assess the importance of PKM2 to cancer cells. Explaining that tumor tissue transformed pyruvate kinase expression from an adult M1 isotope to an embryonic M2 isotope, they conducted immunoblotting and immunohistochemistry analyzes of many cancer lines, cancerous breast cancer samples. colon letters, confirming that PKM2 is the only form of pyruvate kinase found in cancer cells.

The scientists turned off the expression of PKM2 in human cancer lines and the mature M1 form. The conversion from fetal M2 to mature M1 isotope leads to reduced lactate and increased oxygen consumption - a reversal of the Warburg effect.

'We are capable of proving that only the M2-able cells of pyruvate kinase - and glucose metabolism in the way that Otto Warburg described 80 years ago - are capable of producing tumors in mice. " In addition, the scientists have demonstrated that PKM2's ability to interact with phosphotyrosine allows this pyruvate kinase to perform a unique glucose metabolism observed in cancer cells, thereby causing the cells arise tumors in living organisms. "

These findings are consistent with the idea that tumor cells prioritize glucose for purposes other than producing adenosine triphosphate (ATP), the energy source of normal cells.'We suspect that this mechanism has evolved to ensure that fetal tissues only use glucose to grow when they are activated by appropriate growth factor receptor protein-tyrosine kinases. Through the reactivation of PKM2, cancer cells require the use of glucose in the assimilation process. '

'Because we found PKM2 in all cancer cells tested, because this type is not present in most normal adult tissues, and because it plays an important role in tumor formation. , the type of pyruvate kinase is a target for cancer treatments . "

This work was funded by the National Institutes of Health and Damon Runyon Cancer Research Foundation.