Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study shows naturally occurring proteins protect against rapid tumor growth

16.02.2005


Research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) helps explain how a group of angiogenesis inhibitor molecules serve as an important defense mechanism against the development and spread of cancer, offering key insights into why cancerous tumors grow at different rates among different individuals.


The findings, which could help lead to the development of new drug treatments to help keep existing tumors at bay, are reported in the early edition of the Proceedings of the National Academy of Sciences (PNAS) and in the Feb. 22 edition of the publication.


Angiogenesis, the process by which new blood vessels are derived from preexisting capillaries, is considered essential for tumor growth. The "angiogenic switch" is turned on when levels of angiogenesis stimulator molecules (VEGF, bFGF) exceed those of angiogenesis inhibitor molecules. These proteins – which include tumstatin, endostatin and thrombospondin-1 – are naturally present in body fluids or tissues, providing a counterbalance to the stimulator molecules.

Earlier studies by the paper’s senior author Raghu Kalluri, PhD, published in Science and Cancer Cell in 2002 and 2003, respectively, helped to explain the mechanisms by which tumstatin and endostatin prevent the growth of new blood vessels.



Based on these earlier findings, and coupled with two separate clinical observations – that Down syndrome patients have a significantly smaller incidence of cancer than the population-at-large and that nonsymptomatic microscopic tumors exist in the organs of healthy individuals – Kalluri hypothesized that angiogenic inhibitor molecules were acting as tumor suppressors to control the rate of cancer progression.

"For several decades now, autopsies have shown that many people [between ages 40 and 50] who have died of trauma [i.e. automobile accidents, suicide] have tiny dormant tumors in one or more of their organs, though only one percent have been diagnosed with cancer," explains Kalluri, who is the director of the Center for Matrix Biology at BIDMC and Associate Professor of Medicine at Harvard Medical School. "Our goal in this research was to find out if naturally occurring proteins were preventing the recruitment of new blood vessels into the tumors, and thereby keeping the tiny dormant tumors from developing into large malignant tumors. We wanted to better understand the important guards and checkpoints that our bodies possess."

To test the hypothesis that angiogenesis inhibitor molecules were responsible for reining in tumor growth, Kalluri and his colleagues studied the proteins tumstatin, endostatin and thrombospondin-1, natural inhibitors of angiogenesis found in blood, urine and tissues throughout the body. The authors created mice genetically deleted in each of these proteins to help ascertain their normal function in tumor growth.

Their results showed when any one of these inhibitors was removed from the mice, tumors grew at a rate two to three times faster when compared with normal mice. "But even more significant," notes Kalluri, "we found that when two of the inhibitor proteins were simultaneously removed, the tumors grew faster still, suggesting that the body’s own natural capacity to guard against cancer progression plays a role equally as important as genetic defects of cancer cells in whether or not tumors grow and spread."

To demonstrate therapeutic possibilities, the researchers then developed a transgenic mouse that overproduced the endostatin protein in quantities that mimicked Down syndrome patients (a 1.6-fold increase over normal) who, due to an extra copy of chromosome 21, have elevated levels of the protein. As predicted, tumors in this group of mice grew three times more slowly than did tumors in normal mice.

"The evidence that tumor angiogenesis is controlled by endogenous proteins has been accumulating over the past decade, but has depended largely on the use of these molecules that are introduced into tumor-bearing mice," notes Robert Weinberg, PhD, of the Whitehead Institute for Biomedical Research and the Department of Biology at the Massachusetts Institute of Technology (MIT). "The real question has been, however, whether the tissues of the tumor-bearing mouse [and by extension, a human] produce these agents in quantities that truly affect tumor growth. With this paper, we have compelling evidence that a number of these molecules, when produced by the mouse’s own tissues, are able to act to constrain blood vessel growth in the tumors – the final piece of proof needed to demonstrate their importance in preventing the outgrowth of tumors."

"These mice [in the Kalluri study] are the first animals to mimic the protection against cancer which is afforded individuals with Down syndrome who also have a similar increase in endostatin in their blood, and are the most protected against cancer of all humans," adds Judah Folkman, MD, Director of the Vascular Biology Program at Children’s Hospital Boston whose laboratory first proposed the angiogenesis paradigm more than 30 years ago.

"This is a landmark paper because it provides genetic proof that endogenous inhibitors of angiogenesis circulating in the blood may protect us from the disease of cancer and is the first demonstration that a mild increase in one of the circulating angiogenesis inhibitors, endostatin, confers protection against cancer in mice, i.e. reduces the growth rate of tumors by 300 percent," Folkman adds.

"Between nine and 10 million people worldwide die of cancer each year," says Kalluri. "While a lot has been learned of how genetic defects convert normal cells into cancerous cells, much less is known about how the body defends itself against the growth of cancer. Our study helps provide a glimpse into what may be happening. The hope is that this new understanding of cancer growth can eventually lead to the use of these natural proteins as therapies to treat cancer at an early stage, before it becomes a devastating disease."

Bonnie Prescott | EurekAlert!
Further information:
http://www.bidmc.harvard.edu

More articles from Studies and Analyses:

nachricht New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)

nachricht Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>