Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breast tumor stiffness and metastasis risk linked by molecule's movement

21.04.2015

Stiffness drives cancer invasion through previously unknown mechanism

Researchers at the University of California, San Diego School of Medicine and Moores Cancer Center have discovered a molecular mechanism that connects breast tissue stiffness to tumor metastasis and poor prognosis. The study, published April 20 in Nature Cell Biology, may inspire new approaches to predicting patient outcomes and halting tumor metastasis.


In stiffness levels similar to breast cancer (right), cells are better able to invade surrounding tissue and metastasize.

Credit: UC San Diego School of Medicine

"We're finding that cancer cell behavior isn't driven by just biochemical signals, but also biomechanical signals from the tumor's physical environment," said senior author Jing Yang, PhD, associate professor of pharmacology and pediatrics.

In breast cancer, dense clusters of collagen fibers makes the tumor feel stiffer than surrounding tissue. That's why breast tumors are most often detected by touch -- they feel harder than normal breast tissue. But it's also known that increased tumor stiffness correlates with tumor progression and metastasis, as well as poor survival.

To determine how tissue stiffness influences tumor behavior, the team of cancer biologists and bioengineers used a hydrogel system to vary the rigidity on 3D cultures of breast cells from that typically experienced by normal mammary glands to the high stiffness characteristic of breast tumors. They discovered that high stiffness causes a protein called TWIST1 to lose its molecular anchor and move into the cell's nucleus. In the nucleus, TWIST1 activates genes that enable breast cancer cells to invade surrounding tissue and metastasize to other places in the body.

The researchers also compared mouse models of human breast cancer with and without TWIST1's anchor, a protein called G3BP2. Without G3BP2, tumors were more invasive and developed more metastases in the lung, compared to tumors with G3BP2.

The same mechanism plays out in human breast cancers, too, the researchers found. Analysis of human breast cancer patient samples showed that patients with stiffer tumors (meaning tumors with more organized collagen structures) did not survive as long as patients with more compliant tumors with disorganized collagen. Patients with both low G3BP2 and stiffer tumors had even shorter survival times. The correlations were so clear the team could use these factors -- G3BP2 protein levels and collagen organization -- to predict patient outcome.

"Next we want to understand exactly how cells interpret mechanical cues into biological responses," said Laurent Fattet, PhD, a postdoctoral researcher in Yang's lab who led the study, along with former graduate student Spencer Wei. "This cross-talk between a tumor's biomechanical microenvironment and the inter-workings of individual cancer cells may someday provide new therapeutic strategies to slow cancer's spread."

###

Co-authors of this study also include Jeff H. Tsai, Vincent H. Pai, Hannah E. Majeski, Albert C. Chen, Robert L. Sah, and Adam J. Engler, UC San Diego; Yurong Guo, and Susan S. Taylor, Howard Hughes Medical Institute and UC San Diego.

This research was funded, in part, by the National Institutes of Health (grants DP2OD002420-01, 1RO1CA168689, 1R01CA174869, DK54441, P01AG007996, 2T32CA067754, 5T32CA077109), Department of Defense Breast Cancer Program, American Cancer Society, Howard Hughes Medical Institute, ARCS Foundation and Fondation pour la Recherche Médicale.

Media Contact

Heather Buschman
hbuschman@ucsd.edu
619-543-6163

 @UCSanDiego

http://www.ucsd.edu 

Heather Buschman | EurekAlert!

More articles from Health and Medicine:

nachricht TSRI researchers develop new method to 'fingerprint' HIV
29.03.2017 | Scripps Research Institute

nachricht Periodic ventilation keeps more pollen out than tilted-open windows
29.03.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

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...

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

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>