Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breast Cancer Cells Enticed To Spread By "Tumorous Environment" As Well As Genetic Changes

24.10.2012
A new study from Johns Hopkins researchers suggests that the lethal spread of breast cancer is as dependent on a tumor’s protein-rich environment as on genetic changes inside tumor cells.

In a report in the Sept. 25 issue of the Proceedings of the National Academy of Sciences, the scientists conclude that a molecular signal in the protein meshwork surrounding the breast cancer cells may provide the critical trigger to initiate the life-threatening process of metastasis to distant sites in the body.

Moreover, their experiments suggest that the environment surrounding a tumor can even coax healthy breast cells to invade surrounding tissue just as cancer cells do, and that a healthy environment can cause cancer cells to stay put and not spread as they usually do.

“The most dangerous aspect of breast cancer is its ability to spread to distant sites, and most tumors are initially unable to do that,” says Andrew Ewald, Ph.D., assistant professor of cell biology at the Johns Hopkins School of Medicine and member of the Institute for Basic Biomedical Sciences’ Center for Cell Dynamics. Learning more specifically what triggers metastases may provide additional targets for preventing and treating the malignant process that causes cancer deaths, Ewald adds.

It’s widely accepted that cancers acquire the ability to spread through the gradual accumulation of genetic changes, and experiments have also shown that these changes occur in parallel with changes in the protein content and 3-dimensional patterning of the protein meshwork that creates their immediate surroundings. What has been unclear is whether those immediate surroundings play a role in initiating and encouraging cancer’s spread, or whether they are more “effect” then “cause.”

To sort out the contributions of both the genetic changes and the environment, Ewald’s team separated tumor cells from their surroundings by taking fragments of human breast tumors and embedding them in two different commercially available 3-D gels, one that mimics the protein meshwork surrounding healthy mammary tissue and another that mimics tumorous mammary tissue.

The gels are tools often used to study tumor invasiveness. The first was made of proteins that normally create a thin layer around healthy breast tissue, acting as a molecular boundary for it. The second was made entirely of a protein, collagen I, which is found in unusually high concentrations around breast tumors.

If cancer cells are driven to disperse solely because of the genetic changes they carry, the researchers expected to see the tumor fragments behave similarly in both the healthy and tumorous environments. What they saw instead, says Ewald, was a distinct difference. As expected, 88 percent of tumor fragments sent cells crawling into the tumorous meshwork environment, the first step in metastasis known as dissemination. (See video: http://www.cellimagelibrary.org/images/42161) But only 15 percent of tumor fragments sent cells crawling into the normal environment. (See video: http://www.cellimagelibrary.org/images/42160) According to Ewald, these results indicate that the environment around a tumor plays a more direct role in cancer spread than previously thought.

If indeed cells can be enticed outward by the protein environment, the researchers reasoned, that environment might even be powerful enough to coax cells away from healthy breast tissue. To test this idea, they took fragments of both healthy and cancerous mouse mammary glands and placed them in the collagen I gels mimicking a tumor’s environment. Results show that in the tumorous environment, nearly as many of the healthy fragments sent cells dispersing as did the tumorous fragments. (See videos: http://www.cellimagelibrary.org/images/42151 and http://www.cellimagelibrary.org/images/42152)

One notable difference shown in their time-lapse videos was that healthy cells only exited the normal tissue fragments for a short period of time, while cancer cells continued to exit the tumor fragments throughout the whole test period.

To learn why healthy cells stopped exiting normal tissue fragments sooner, the researchers analyzed the proteins on the cells that were in direct contact with the meshwork gels. In breast tissue, a thin protein layer normally forms a boundary between cells and their environment. When both healthy and tumorous tissue fragments were surgically removed prior to the experiments, this boundary was disrupted, allowing breast cells to directly contact the protein meshwork beyond the boundary. In healthy mammary gland fragments, the team found that the “self-corrective behavior” coincided with the re-creation of this protein boundary.

“This tells us that tumors continue to listen to their environments,” Ewald says. “Our data suggest that tumors with genetic changes that favor cancer spread may not disperse until they are within a permissive environment.” A dispersal-permissive environment is enough to provoke invasive behavior in all mammary tissue, healthy and cancerous, Ewald explains, and the difference between the two can be a single genetic change that allows the dispersal to continue unchecked.

Other authors of the report include Kim-Vy Nguyen-Ngoc, Kevin Cheung, Eliah Shamir and Ryan Gray from The Johns Hopkins University; Audrey Brenot and Zena Werb from the University of California, San Francisco; and William Hines and Paul Yaswen from Lawrence Berkeley National Laboratory.

The research was supported by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins and by grants from the National Cancer Institute (R01CA056721, R01CA138818, U01CA155758, U54CA151838, P50CA88843), the National Institute of Environmental Health Sciences (U01ES019458) and the Safeway Foundation Award for Breast Cancer Research.

Catherine Kolf | Newswise Science News
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>