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 Smart Data Transformation – Surfing the Big Wave
02.12.2016 | Fraunhofer-Institut für Angewandte Informationstechnik FIT

nachricht Climate change could outpace EPA Lake Champlain protections
18.11.2016 | University of Vermont

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: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>