Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer Cells Accelerate Aging and Inflammation in the Body to Drive Tumor Growth

30.05.2011
Researchers at the Kimmel Cancer Center at Jefferson have shed new light on the longstanding conundrum about what makes a tumor grow—and how to make it stop. Interestingly, cancer cells accelerate the aging of nearby connective tissue cells to cause inflammation, which ultimately provides “fuel” for the tumor to grow and even metastasize.

This revealing symbiotic process, which is similar to how muscle and brain cells communicate with the body, could prove useful for developing new drugs to prevent and treat cancers. In this simple model, our bodies provide nourishment for the cancer cells, via chronic inflammation.

“People think that inflammation drives cancer, but they never understood the mechanism,” said Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Jefferson Medical College of Thomas Jefferson University and a member of the Kimmel Cancer Center. “What we found is that cancer cells are accelerating aging and inflammation, which is making high-energy nutrients to feed cancer cells.”

In normal aging, DNA is damaged and the body begins to deteriorate because of oxidative stress. “We are all slowly rusting, like the Tin-man in the Wizard of Oz,” Dr. Lisanti said. “And there is a very similar process going on in the tumor’s local environment.” Interestingly, cancer cells induce “oxidative stress,” the rusting process, in normal connective tissue, in order to extract vital nutrients.

Dr. Lisanti and his team previously discovered that cancer cells induce this type of stress response (autophagy) in nearby cells, to feed themselves and grow. However, the mechanism by which the cancer cells induce this stress and, more importantly, the relationship between the connective tissue and how this “energy” is transferred was unclear.

“Nobody fully understands the link between aging and cancer,” said Dr. Lisanti, who used pre-clinical models, as well as tumors from breast cancer patients, to study these mechanisms. “What we see now is that as you age, your whole body becomes more sensitive to this parasitic cancer mechanism, and the cancer cells selectively accelerate the aging process via inflammation in the connective tissue.”

This helps explain why cancers exist in people of all ages, but susceptibility increases as you age. If aggressive enough, cancer cells can induce accelerated aging in the tumor, regardless of age, to speed up the process.

The researchers’ findings were published online June 1st in the journal Cell Cycle in three separate papers.

One paper analyzes the gene profiles of the laser-captured connective tissue, associated with lethal tumors, in human breast cancer patients. In this paper, lethal cancers show the same gene expression pattern associated with normal aging, as well as Alzheimer’s disease. In fact, these aging and Alzheimer’s disease signatures can identify which breast cancer patients will undergo metastasis. The researchers find that oxidative stress is a common “driver” for both dementia and cancer cell spreading.

In another study, the researchers explain that cancer cells initiate a “lactate shuttle” to move lactate—the “food”—from the connective tissue to the cancer cells. There’s a transporter that is “spilling” lactate from the connective tissue and a transporter that then “gobbles” it up in the cancer cells.”

The implication is that the fibroblasts in the connective tissue are feeding cancer cells directly via pumps, called MCT1 and MCT4, or mono-carboxylate transporters. The researchers see that lactate is like “candy” for cancer cells. And cancer cells are addicted to this supply of “candy.”

“We’ve essentially shown for the first time that there is lactate shuttle in human tumors,” said Dr. Lisanti. “It was first discovered nearly 100 years ago in muscles, 15 years ago in the brain, and now we’ve shown this shuttle also exists in human tumors.”

It’s all the same mechanism, where one cell type literally “feeds” the other. The cancer cells are the “Queen Bees,” and the connective tissue cells are the “Worker Bees.” In this analogy, the “Queen Bees” use aging and inflammation as the signal to tell the “Worker Bees” to make more food.

Researchers also identified MCT4 as a biomarker for oxidative stress in cancer-associated fibroblasts, and inhibiting it could be a powerful new anti-cancer therapy.

“If lethal cancer is a disease of “accelerated aging” in the tumor’s connective tissue, then cancer patients may benefit from therapy with strong antioxidants and anti-inflammatory drugs,” said Dr. Lisanti. “Antioxidant therapy will “cut off the fuel supply” for cancer cells.” Antioxidants also have a natural anti-inflammatory action.

References:
http://www.landesbioscience.com/journals/cc/article/15674/
http://www.landesbioscience.com/journals/cc/article/15659/
http://www.landesbioscience.com/journals/cc/article/15675/
Disclosure: Dr. Michael Lisanti serves as on the editorial board of Cell Cycle. No person at Thomas Jefferson University was involved in the peer review process or final disposition for this article.

Steve Graff | EurekAlert!
Further information:
http://www.jefferson.edu

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>