Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MicroRNA regulates cancer stem cells

17.12.2007
One of the biggest stories in cancer research over the past few years has been, unexpectedly, stem cells. Not embryonic stem cells, but tumor stem cells. These mutated cells, which live indefinitely and can seed new tumors, are now suspected of causing many, if not all, cancers. What is worse, these persistent cells are not killed by chemotherapy or other current treatments.

Their survival might explain why tumors frequently recur or spread after treatment. Increasingly, researchers view the challenge of getting rid of these bad seeds as the key to treating cancer far more effectively. However, because they are extremely rare, even in large tumors, studying them has been difficult.

Now, researchers have devised a way to generate large numbers of human breast cancer stem cells in mice and have discovered a genetic switch that regulates critical properties of the cells. The regulator, which belongs to a class of molecules called microRNAs (microRNAs), pushes the stem cells to become more differentiated and less tumorigenic through its ability to switch off particular genes.

“People know that microRNAs are important regulators of cell differentiation, but nobody has shown that they regulate the critical properties of cancer stem cells, or any kind of stem cells,” says Judy Lieberman, an investigator at the Immune Disease Institute and Harvard Medical School professor of pediatrics at Children’s Hospital Boston. Lieberman and Erwei Song, a former postdoc in her lab now working as a breast cancer surgeon at Sun Yat-Sen University in Guangzhou, China, are the senior investigators on the work, which appears in the Dec. 14 issue of Cell.

By showing that microRNAs can rein in tumor stem cells, the work suggests a novel way to target these cells to treat cancer with therapeutic RNAs, a promising new class of medicine under development for many diseases.

In the study, Song and first author Fengyan Yu started working in China to isolate breast cancer stem cells from freshly removed tumors. Because cancer stem cells resist chemotherapy, the researchers predicted that breast tumors from women who had received such treatment before surgery might be enriched with stem-like cells, and their experiments confirmed this idea. In tumors from untreated women, less than 1 in 250 cells had the cell surface markers and growth characteristics of stem cells; in treated tumors, the number rose to 1 in 17.

The finding gave Song and Yu the idea of trying to generate larger quantities of tumor stem cells by growing human breast cancer cells in immunosuppressed mice dosed with a chemotherapeutic agent. After three months of such a regimen, nearly 75 percent of the cells in the retrieved tumors displayed the properties of stem cells: they had the expected cell surface markers, were highly tumorigenic and metastatic in mice, were relatively drug resistant, and could be induced to differentiate into multiple kinds of breast tissue cells.

With a ready supply of cancer stem cells, the researchers were able to measure levels of microRNAs, small gene regulators that are known to influence a gene’s ability to create proteins important for cell growth and differentiation. They found that cancer stem cells contained low amounts of several microRNAs compared to more mature tumor cells or stem cells that had differentiated in culture.

They zeroed in on a tumor-supressing microRNA called let-7. When the team activated let-7 in the stem cells, they lost their ability to self-renew and began to differentiate. The cells also became less able to form tumors in mice or to metastasize. Further studies showed that let-7 did this by switching off two cancer-related genes: the oncogene Ras, and HMG2A, which when switched off caused the cells to differentiate.

If this finding applies to other tumor types, let-7 may offer a unique opportunity to attack tumor stem cells using therapeutic RNA. Delivery of the let-7 RNA to tumors could potentially deplete stem cells by pushing them down the path of differentiation. Using small RNAs to treat disease is a topic Lieberman is quite familiar with—in 2003, her lab was the first to show therapeutic RNAs could work in an animal model of liver disease, and their work has since focused on devising methods for targeting RNAs to all kinds of cells. Yu, now a visiting student in the Lieberman lab, is looking at ways to deliver the let-7 RNA mimics to stem cells.

“One of the fundamental problems of all the therapies that we have is that they are not doing anything to these cells,” Lieberman says. “If those turn out to be the cells that go on and form metastases and are resistant to chemotherapy and are responsible for relapses, and if your therapy isn’t dealing with those cells and is, in fact, selecting for them, that is very worrisome.”

David Cameron | EurekAlert!
Further information:
http://www.hms.harvard.edu
http://www.cbrinstitute.org/labs/lieberman/index.html

Further reports about: Lieberman MicroRNA RNA Regulator Stem differentiate let-7 stem cells

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>