Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tumor surroundings are shown to affect progression of different cancer subtypes

28.05.2015

Treatments may need to be tailored not just to specific cancer types but also to factors distinguishing environments in which they develop

Our environment can have a major impact on how we develop, and it turns out it's no different for cancer cells. In work published today in Neoplasia, a team of researchers led by Associate Professor Mikala Egeblad at Cold Spring Harbor Laboratory (CSHL) found that two different mouse models of breast cancer progressed differently based on characteristics of the tumor microenvironment - the area of tissue in which the tumor is embedded.


Mikala Egeblad's team showed in mice that the progression of different types of breast cancer was influenced differently by the tissue -- the so-called tumor microenvironment -- in which the tumor is embedded. The tumor microenvironment contains many factors, including immune cells and blood vessels, that communicate with cancer cells and can promote tumor growth. On the left, a breast cancer type called luminal; on the right, a type called triple-negative/basal. The luminal microenvironment has less fibrosis (scar tissue, colored purple) and contains few inflammatory cells embedded within these fibrotic areas or in the surrounding fatty tissue (white). The triple-negative microenvironment contains more inflammatory cells and more fibrosis. Targeting a protein called MMP9, which promotes cancer and is linked with poor prognosis, slowed the course of the triple-negative/basal breast cancer, the one with the more profoundly altered microenvironment, but had no impact on the luminal cancer.

Credit: Egeblad Lab, CSHL

The tumor microenvironment includes cells and extracellular molecules that support the tumor's growth. Egeblad and her team looked at two types of breast cancer driven by different mutations, and found very different microenvironments. One common factor was the presence of an extracellular protein called matrix metalloproteinase 9 (MMP9). It was expressed at similar levels in tumors from both breast cancer mouse models.

MMP9 previously has been linked to the progression of many types of cancers. When the researchers deleted the Mmp9 gene, they found that the absence of the MMP9 protein delayed tumor onset only in one mouse model, and had no effect in the other model.

Egeblad and her team found that whether MMP9 promoted cancer or not depended on the tumor microenvironment. Specifically, on the presence of another molecule that MMP9 is known to act on, called insulin-like growth factor binding protein 1 (IGFBP-1). "If IGFBP-1 is not there, MMP9 didn't really have an effect, but if it's there, then MMP9 has a role," says Egeblad. This suggests that IGFBP-1 interacts with MMP9 to promote tumor formation.

IGFBP-1 binds insulin-like growth factors (IGFs), which play a role in promoting cancer proliferation. "IGFBP-1 keeps the growth factors sequestered so they can't act on the cancer cells and can't make them proliferate," Egeblad says. "But if MMP9 is present, it degrades these IGFBPs and releases the growth factors." The release of the IGFs then accelerates cancer progression.

Egeblad and her team looked in human cancer databases to see if the interaction between MMP9 and IGFBPs predicted breast cancer prognosis in humans. "We found that IGF-binding proteins are associated with a good prognosis, but if MMP9 is also present, there's no longer good association with survival," Egeblad says.

The study's results have implications for anti-cancer drugs that target MMPs, and may explain why previous clinical trials using MMP inhibitors have failed, Egeblad says. "Maybe you can actually think about using these inhibitors if you better understand their biology," she says. The new study suggests that trials of MMP inhibitors could focus on patients whose tumor microenvironment contains IGFBPs, she says.

More broadly, the research suggests that it may not be enough to see if a particular drug target is present in a certain type of cancer; researchers may also need to look for the presence of the molecules that the drug target acts upon. "It complicates things, but I think biologically it makes a lot of sense. You really need to dig deep and understand mechanistically what the target does," Egeblad says.

The lab's next goal is to look more generally at the differences in microenvironments in different types of cancer. "What we're starting to learn now is that the microenvironments are different in different tumors, and that there is really a very intricate interplay between what's driving the mutations in cancer cells and the type of microenvironment they build around themselves," Egeblad says.

###

This work was supported by funds from the NIH (R01CA057621), the Breast Cancer Alliance, the Long Island 2 Day Walk to Fight Breast Cancer, the Manhasset Women's Coalition Against Breast Cancer, the University of Copenhagen, the Augustinus Fonden, the Dagmar Marshalls Fond, the European Association for Cancer Research, and a postdoctoral fellowship from the U.S. Department of Defense Breast Cancer Research Program.

"Presence of insulin-like growth factor binding proteins correlates with tumor-promoting effects of matrix metalloproteinase 9 in breast cancer " appears online in Neoplasia on May 27, 2105, 2015. The authors are: Jae-Hyun Park, Ph.D.; Morten G Rasch, Ph.D.; Jing Qiu; Ida K Lund, Ph.D.; Mikala Egeblad. The paper can be obtained online at: http://neoplasia.org/article/S1476-5586(15)00047-0/fulltext

About Cold Spring Harbor Laboratory

Celebrating its 125th anniversary in 2015, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory is more than 600 researchers and technicians strong. The Meetings & Courses Program hosts more than 12,000 scientists from around the world each year on its campuses in Long Island and in Suzhou, China. The Laboratory's education arm also includes an academic publishing house, a graduate school and programs for middle and high school students and teachers. For more information, visit http://www.cshl.edu

Media Contact

Peter Tarr
tarr@cshl.edu
516-367-8455

 @CSHLnews

http://www.cshl.edu 

Peter Tarr | EurekAlert!

More articles from Health and Medicine:

nachricht Researchers image atomic structure of important immune regulator
11.12.2018 | Brigham and Women's Hospital

nachricht Potential seen for tailoring treatment for acute myeloid leukemia
10.12.2018 | University of Washington Health Sciences/UW Medicine

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: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

 
Latest News

Electronic evidence of non-Fermi liquid behaviors in an iron-based superconductor

11.12.2018 | Physics and Astronomy

Topological material switched off and on for the first time

11.12.2018 | Materials Sciences

NIST's antenna evaluation method could help boost 5G network capacity and cut costs

11.12.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>