Navigation Links
Study helps explain fundamental process of tumor growth
Date:3/12/2008

BOSTON Nearly 80 years ago, scientist Otto Warburg observed that cancer cells perform energy metabolism in a way that is different from normal adult cells. Many decades later, this observation was exploited by clinicians to better visualize tumors using PET (positron emission technology) imaging. But it has not been known exactly how tumor cells perform this alternate metabolic feat, nor was it known if this process was essential for tumor growth.

Now, two papers appearing in the March 13 issue of the journal Nature help answer these questions. Led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Harvard Medical School, the papers find that the metabolic process that has come to be known as the Warburg effect is essential for tumors rapid growth, and identifies the M2 form of pyruvate kinase (PKM2), an enzyme involved in sugar metabolism, as an important mechanism behind this process. This discovery could provide a target for the development of future cancer therapies.

With this study we have answered a fundamental question regarding the ability of tumor cells to rapidly grow and proliferate, explains senior author Lewis Cantley, PhD, Director of the Cancer Center at BIDMC and Professor of Systems Biology at Harvard Medical School.

Metabolic regulation in rapidly growing tissues, such as fetal tissue or tumors, is different from that of normal adult tissue, Cantley explains. Through aerobic glycolysis, or the Warburg effect, cancer cells produce energy by taking up glucose at much higher rates than other cells while, at the same time, using a smaller fraction of the glucose for energy production. This allows cancer cells to function more like fetal cells, promoting extremely rapid growth. This unique metabolic property of cancer cells has led to the success of PET imaging as a means of cancer detection; because radioactive glucose injected into patients prior to the imaging exam is preferentially taken up by glucose-hungry tumor cells, the areas of high glucose uptake are displayed dramatically on the PET scan.

Using a novel proteomic screen to identify new phosphotyrosine binding proteins, Cantley and his colleagues first determined that PKM2 can bind to phosphotyrosine-containing peptides. We observed that in contrast to the forms of pyruvate kinase found in most normal adult tissues, only PKM2, which is found in fetal cells, interacted with phosphotyrosine, explains Cantley. This finding was particularly interesting because previous reports had shown that this M2 form was the pyruvate kinase form used by all cancer cells.

In order to understand the implications of this discovery, Cantley and his coauthors next embarked upon experiments to evaluate the importance of PKM2 to cancer cells. Reasoning that tumor tissue switches pyruvate kinase expression from an adult M1 isoform to the embryonic M2 isoform, they performed immunoblotting and immunohistochemistry analysis of numerous cancer cell lines, breast cancer models and human colon cancer, confirming that PKM2 was the only form of pyruvate kinase found in cancerous tissue.

The authors then knocked down PKM2 expression in human cancer cell lines and expressed the adult M1 form instead. This switch from the fetal M2 form to the adult M1 isoform led to reduced lactate production and increased oxygen consumption a reversal of the Warburg effect.

We were able to show that only cells which express the M2 form of pyruvate kinase and metabolize glucose in the way described by Otto Warburg 80 years ago had the ability to form tumors in mice, notes Cantley. In addition, the investigators demonstrated that it is the ability of PKM2 to interact with phosphotyrosine that enables this form of pyruvate kinase to promote the unique glucose metabolism seen in cancer cells, thereby allowing these cells to make tumors in vivo.

The findings are consistent with the idea that tumor cells preferentially use glucose for purposes other than making adenosine triphosphate (ATP), the energy currency used by normal cells. We suspect that this mechanism evolved to ensure that fetal tissues only use glucose for growth when they are activated by appropriate growth factor receptor protein-tyrosine kinases, adds Cantley. By re-expressing PKM2, cancer cells acquire the ability to use glucose for anabolic processes.

Because PKM2 is found in all of the cancer cells that we have examined, because it is not found in most normal adult tissues, and because it is critical for tumor formation, this form of pyruvate kinase is a possible target for cancer therapy, he adds.


'/>"/>

Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

Related medicine news :

1. Protein deficiency leads to faster fat burning in mice, study shows
2. Study Finds Naturopathic Care for Chronic Low-Back Pain to be Efficacious, Cost-Effective
3. New AHIP Study in Health Affairs Challenges Previous Assumptions About Medigaps Impact on Medicare Costs
4. MHA to Release Findings of Independent Long Term Care Member Study
5. Henry Ford Hospital to study effectiveness of a new procedure that may help emphysema suffers
6. Radiologist Leora Lanzkowsky Study Suggests ...
7. Cepheid Comments on Study Regarding MRSA Surveillance Reported in the Journal of the American Medical Association
8. Life Recovery Systems Study of Heart Attack With ThermoSuit(R) System
9. Gender bias may affect care of people with osteoarthritis, study finds
10. Lung damage in babies with congenital heart disease under study
11. The hand cant be fooled, study shows
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/24/2017)... ... 24, 2017 , ... Judy Buchanan, co-owner of Serenity Natural ... Judy says, “I am passionate about sharing Reiki as a holistic, complementary therapy ... challenging time.” , A Certified Medical Reiki™ Master trained by Raven Keys Medical ...
(Date:3/24/2017)... ... March 24, 2017 , ... “End Time GPS”: a dauntless and ... “End Time GPS” is the creation of published author, Wesley Gerboth, a World ... military munitions and space-vehicle projects. Now, at age ninety-one, he shares the Wisdom God ...
(Date:3/24/2017)... ... 24, 2017 , ... “The Communion of Saints: A Pastor’s ... in congregations across the United States. “The Communion of Saints” is the ... has served congregations in seven states throughout his long career of devotion to ...
(Date:3/23/2017)... ... 2017 , ... In 2016 the World Health Organization declared the Zika virus ... Zika-related cases in the Americas within the next year. Lyme disease is one of ... skyrocketing to an estimated 329,000. Yet, Zika, Lyme and other insect borne illnesses are ...
(Date:3/23/2017)... ... March 23, 2017 , ... The physicians of KSF Orthopaedic Center PA ... Area. The new location is located at 2255 E. Mossy Oaks Rd., Suite 440, ... newest location will provide patients living in the north Houston area (The Woodlands, Conroe, ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... 24, 2017 Global Ampoules Market ... definitions, classifications, applications and industry chain structure. The Ampoules ... development history, competitive landscape analysis, and major regions, development ... ... 105 pages providing 10 company profiles and 183 tables ...
(Date:3/24/2017)... Research and Markets has announced the addition of the ... to their offering. ... report provides separate comprehensive analytics for the US, Canada ... Asia-Pacific , Latin America , and Rest ... through 2022. Also, a six-year historic analysis is provided for these markets. ...
(Date:3/24/2017)...  Eli Lilly and Company (NYSE: ... million in its U.S. operations in 2017. The ... including research laboratories, manufacturing sites, and general and ... demand for Lilly products, as well as its ... cancer, pain, diabetes and other unmet medical needs.  ...
Breaking Medicine Technology: