Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Taming physical forces that block cancer treatment

21.09.2012
MGH study identifies components responsible for therapy-blocking solid stress, suggests therapeutic strategies

It's a high-pressure environment within solid tumors. Abnormal blood and lymphatic vessels cause fluids to accumulate, and the uncontrolled proliferation of cancer cells within limited space leads to the buildup of what is called solid stress.

Both types of pressure can interfere with the effectiveness of anticancer treatments, but while strategies have been developed that reduce fluid pressures, little has been known about the impact of solid stress or potential ways to alleviate it. Now a Massachusetts General Hospital (MGH) research team has identified factors that contribute to solid stress within tumors, suggesting possible ways to alleviate it, and has developed a simple way to measure such pressures.

"Traditionally cancer research has focused on cancer cells and, more recently, on the biochemical microenvironment of tumors," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and senior author of the study in the Sept. 18 issue of Proceedings of the National Academy of Sciences. "Our work shows that the physical or mechanical microenvironment plays an equally important role in tumor progression and treatment resistance."

Jain and his colleagues have been leaders in understanding the impact of elevated fluid pressures that make it difficult for drugs to enter and permeate tumors. Their work showed that fluid pressures are relieved when antiangiogenesis drugs normalize the abnormal blood vessels characteristically found within solid tumors, improving the effectiveness of other anticancer therapies. But that approach can only work if vessels have not been squeezed shut by solid stress in surrounding tissues. In recent studies Jain's team showed that solid stress also increases the invasiveness of cancer cells.

The current study was designed to develop techniques that measure solid stress in tumors, to identify factors that contribute to the generation of this solid stress and to determine whether previously compressed blood vessels would open when stress-inducing components were depleted. Based on predictions from mathematical models, the MGH-based team developed a remarkably simple way to measure solid stress within tumor tissues.

In experiments using both tumors experimentally grown in mice and tumors removed from human patients, the researchers found that, when a solid tumor is cut in two, each segment begins to swell along the sliced surface, releasing stored solid stress. In contrast, when a sample of normal tissue is cut in two, the separated halves of tissue retain their size and shape (links to video files below). Measuring the extent of shape relaxation along with other mechanical properties of tumor tissue enabled calculation of the amount of solid stress within a tumor sample.

Sample of breast tumor grown in mouse expands after cutting, releasing solid stress
http://www.pnas.org/content/suppl/2012/08/29/1213353109.DCSupplemental/sm01.mov

Sample of normal mouse kidney tissue, showing no change in shape after cutting
http://www.pnas.org/content/suppl/2012/08/29/1213353109.DCSupplemental/sm02.mov
Additional experiments utilizing the newly developed technique identified several components that contribute to increased solid stress within tumors, including the proliferation not only of cancer cells but also of fibroblasts and other components of the tumor's extracellular matrix. In pancreatic tumors implanted into mice, the researchers showed that inhibition of a pathway leading to the growth of fibroblasts reduced solid stress associated with tumor growth and opened up compressed blood and lymphatic vessels, which could both relieve fluid pressure and improve the delivery of chemotherapy drugs.
The authors note that their results may explain why the use of antiangiogenesis drugs has not improved treatment of highly fibrotic tumors – including dangerous pancreatic, lung and breast cancers – and suggest that a strategy targeting both aspects of intratumor pressure should be explored. "Now that we have seen how tumors exploit physical forces to facilitate progression and treatment resistance, we need to learn how to tame these fluid and solid forces to improve treatment outcomes," says Jain, the Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School. "We urgently need to identify safe pharmaceutical agents that reduce solid stress and then add them judiciously to current treatments."

Co-lead authors of the PNAS paper are Triantafyllos Stylianopoulos, PhD, and John D. Martin of the Steele Laboratory. Additional co-authors are Vikash Chauhan, Saloni Jain, Benjamin Diop-Frimpong, Yves Boucher, PhD, and Lance Munn, PhD, Steele Lab; Nabeel Bardeesy, PhD, MGH Center for Cancer Research; Barbara Smith, MD, MD, and Cristina Ferrone, MD, MGH Department of Surgery; and Francis J. Horniceki, MD, PhD, MGH Orthopaedic Oncology. The study was supported by grants from the National Institutes of Health and the Department of Defense.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org/

More articles from Studies and Analyses:

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New bioimaging technique is fast and economical

21.08.2017 | Medical Engineering

Silk could improve sensitivity, flexibility of wearable body sensors

21.08.2017 | Materials Sciences

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>