Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Replacing absent microRNAs could make tumors less invasive, more treatable

02.04.2008
One group of small, non-coding RNA molecules could serve as a marker to improve cancer staging and may also be able to convert some advanced tumors to more treatable stages, report a University of Chicago-based research team in the April 1, 2008, issue of the journal Genes & Development.

Carcinomas are cancers that develop from epithelial tissue, which lines internal and external body surfaces. When normal cells are transformed into cancer cells, this epithelial tissue can take on the characteristics of embryonic tissue, known as mesenchymal tissue, which is comprised of unspecialized cells that will develop, as the embryo matures, into more specialized tissues.

That process also goes in reverse. Epithelial to mesenchymal transition (EMT) occurs, for example, during wound healing. In cancer, however, this process can produce invasive and mobile cells that can pass through membranes and travel to distant sites, where they seed new tumors.

"There are a bewildering numbers of pathways or stimuli that can either trigger EMT or reverse that process," said study author Marcus E. Peter, PhD, professor in the Ben May Department for Cancer Research at the University of Chicago. "What we have identified is a master regulator of EMT that is probably controlled by many of these stimuli."

Peter and colleagues showed that this master regulator consists of a specific group of microRNAs, a family called miR-200. MicroRNAs are tiny RNA molecules that have very important roles in gene regulation. They have multiple targets and act mainly by attaching themselves to specific sites in messenger RNA to prevent the production of proteins.

The authors studied a standard panel of 60 established human tumor cell lines representing nine different human cancers, as well as several specimens of human primary ovarian cancer. They showed that miR-200 was always present in epithelial (less invasive) and not in mesenchymal (more invasive) types of tumors.

"The importance of this finding is, first, that miR-200 may represent a good marker to stage cancer," Peter said, and "second, that reintroducing miR-200 into late cancer cells could provide a new form of treatment, preventing these cells from going through EMT and becoming more invasive."

Physicians already have a set of fairly reliable markers for carcinoma. Tumors with high levels of E-cadherin tend to be tightly tethered to nearby cells and less likely to break free and travel to other sites. Those with high Vimentin levels represent mesenchymal cells able to pass though other tissues.

Peter and colleagues found that miR-200 added mechanistic depth to those markers. Every tumor cell line the researchers tested that had the epithelial marker E-cadherin and not the mesenchymal marker Vimentin, had high amounts of miR-200. Every cell line with high Vimentin and no E-cadherin had no detectable miR-200.

"So we were able to show a complete correlation between miR-200 and E-cadherin/Vimentin expression," Peter added.

The authors found that miR-200 microRNAs helped regulate EMT transition. They bind directly to non-coding regions in the RNA of ZEB1 and ZEB2, known blockers of E-cadherin transcription. Both ZEB proteins have previously been implicated in human malignancies, ZEB1 in aggressive colorectal and uterine cancers, and ZEB2 in advanced stages of ovarian, gastric and pancreatic tumors.

By inhibiting miR-200, Peter and his coworkers could induce EMT. More important, by introducing miR-200, they managed to activate production of E-cadherin protein and reverse tumors from a more-invasive mesenchymal into a less-invasive epithelial form.

"In a previous paper we found that another micro RNA, let-7, drives tumor progression at an earlier stage," Peter said. "Let-7 appears to be a key player in preventing a cancer from becoming more aggressive. Now we want to figure out how these two micro RNAs work together to regulate carcinogenesis."

Once they understand this process, they want to use these microRNAs to treat cancer. Both microRNA families have the connection to drug resistance as well as to cancer stem cells, sub-population of cancer cells that have self-renewal properties and the ability to give rise to new tumors that are more resistant to current therapy.

"Our aim is not only to make tumors less invasive by reintroducing let-7 and miR-200," explained Peter. "We hope that we'll make tumors more sensitive to drugs and be able to target the stem cell population, which gives tumors their renewal capacity."

"The idea is a two-hit strategy," Peter said, "hit them first with the microRNA and make those drug-resistant cells sensitive again, then hit them again with low levels of conventional chemotherapy."

John Easton | EurekAlert!
Further information:
http://www.uchospitals.edu

Further reports about: E-Cadherin EMT Protein RNA epithelial invasive mesenchymal miR-200

More articles from Life Sciences:

nachricht Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie

nachricht Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Molecular Force Sensors

20.09.2017 | Life Sciences

Producing electricity during flight

20.09.2017 | Power and Electrical Engineering

Tiny lasers from a gallery of whispers

20.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>