Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover specific tumor environment that triggers cells to metastasize

22.11.2017

A team of bioengineers and bioinformaticians at the University of California San Diego have discovered how the environment surrounding a tumor can trigger metastatic behavior in cancer cells. Specifically, when tumor cells are confined in a dense environment, the researchers found that they turn on a specific set of genes and begin to form structures that resemble blood vessels.

In the past, physicians observed these blood vessel-like structures in the clinic--a phenomenon called vascular mimicry, which is associated with some of the most aggressive types of cancers. But they didn't understand what caused this transformation.


This is a Breast cancer cell are grown in a highly dense 3-D collagen matrix. After 7 days the cells form networks that resemble the early stages of blood vessel development. Images show representative structures observed in these environments after satining for cells nuclei (blue) and the cell's cytoskeleton (green). Similar structures have been observed in tumor patient samples and have been referred to as vasculogenic mimicry.

Credit: University of California San Diego

The study adds to researchers' knowledge of how the metastatic process may be initiated. "We are good at targeting tumor growth, but we do not know enough about metastasis," said Stephanie Fraley, a professor of bioengineering at the University of California San Diego and the leader of the study.

Metastatic spread of tumor cells from one location in the body to another is the cause of 90 percent of cancer-related deaths. The set of genes that the researchers discovered, called a gene module, was able to predict patient life expectancy and whether tumors will metastasize across nine types of cancer, including breast, lung, pancreatic, and kidney cancers.

This gene module could be used to help determine whether patients are suffering from an aggressive type of cancer and inform the decisions patients and their physicians make when choosing specific therapies.

Researchers detail their findings in the Nov. 21 issue of Nature Communications.

The researchers were able to make their observations by placing the malignant cells in a custom 3D collagen matrix that they built. They found that the cells turned into structures that mimic blood vessels when surrounded by the matrix made of short fibers and small pores (as opposed to long fibers and large pores) and that this phenomenon was independent of other physical features of the matrix such as stiffness. This finding came as a surprise.

"We thought that putting cells into this more constrained environment would prevent their spread," said Daniel Ortiz Velez, the study's first author and a Ph.D. student in Fraley's lab. "But the opposite happened."

The cells do not exhibit this behavior in traditional petri dishes, the researchers said.

"It's critical to have the cells surrounded by a 3D environment that mimics what happens in the human body," Fraley said.

Drilling further, researchers found that the cells' behavior is caused by a specific gene module, which they named collagen-induced network phenotype, or CINP. Putting these cells into a constrained environment essentially rewrites their gene expression. "It's almost like the matrix is encoding the gene module," Fraley said.

In addition, researchers looked for this gene module in a range of human cancer gene expression and histology databases, which contain records of the microscopic structure of tissues. The presence of the module was a strong predictor of whether the cancer was likely to metastasize aggressively, after controlling for other factors, such as the patient's age.

This makes sense, because the channels built by the malignant cells allow blood to flow to tumors without coagulating and helps bring in nutrients. Researchers have speculated that this also makes it easier for cancer cells to spread through the patient's blood. Other studies have shown that when cancer cells are connected, it improves their chances of spreading to distant sites in the body.

Next steps include testing the method in animal studies and additional human datasets. Researchers also will be looking for molecular targets to prevent the transformation of the cells.

Researchers are in talks to license their method.

###

The study was funded by Fraley's NSF CAREER Award, Burroughs Wellcome Fund Career Award at the Scientific Interface, and UC San Diego Frontiers of Innovation Scholars Program grant as well as co-author Professor Hannah Carter's NIH Director's Early Independence Award.

3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry

Authors: Daniel Ortiz Velez, T. Goshia, C.L. Chute, A. Han, Stephanie Fraley, Department of Bioengineering, UC San Diego; B. Tsui, Bioinformatics and Systems Biology Program, UC San Diego, Hannah Carter, Department of Medicine, Moores Cancer Center, Uc San Diego

doi:10.1038/s41467-017-01556-7

Media Contact

IOANA PATRINGENARU
ipatrin@eng.ucsd.edu
858-822-0899

 @UCSanDiego

http://www.ucsd.edu 

Ioana Patringenaru | EurekAlert!

Further reports about: 3D blood cancer cells fibers malignant cells metastasize

More articles from Life Sciences:

nachricht Researchers find new mutation in the leptin gene
24.06.2019 | Texas Biomedical Research Institute

nachricht Straight to the heart
24.06.2019 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

'Sneezing' plants contribute to disease proliferation

24.06.2019 | Agricultural and Forestry Science

Researchers find new mutation in the leptin gene

24.06.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>