Newly Identified Gene Powerful Predictor Of Colon Cancer Metastasis - Low Gene Activity - Higher Survival Rate

Cancer Researchers at the Max Delbruck Center for Molecular Medicine (MDC) Berlin-Buch and the Charite - Universitats Medizin Berlin (Germany) have identified a gene which enables them to predict for the first time with high probability if colon cancer is going to metastasize. Assistant Professor Dr. Ulrike Stein, Professor Peter M. Schlag, and Professor Walter Birchmeier were able to demonstrate that the gene MACC1 (Metastasis-Associated in Colon Cancer 1) not only promotes tumor growth but also the development of metastasis.When MACC1 gene activity is low, the life expectancy of patients with colon cancer is longer in comparison to patients with high MACC1 levels. (Nature Medicine, doi: 10.1038/nm.1889)*.

According to the National Institutes of Health in Bethesda, Maryland, USA, more than 108,000 people developed colon cancer in the US in 2008. Despite surgery, chemo- and radiotherapy, only 50 percent of patients can be cured because 20 percent of the patients have already developed metastasis by the time their colon cancer is diagnosed. In addition, one-third of patients whose treatment of the original colon cancer was successful will, nevertheless, go on to develop metastasis.

The MDC and Charité researchers are convinced that the identification of the MACC1 gene will aid medical doctors in identifying those patients as early as possible who are at high risk of developing life-threatening metastasis in the liver and the lungs. As a result, more intensive treatment and follow-up care could be offered to high risk patients.

MACC1 turns on a signaling pathway which is important for tumor growth and the formation of metastasis. Researchers call this pathway HGF/Met signaling pathway. Once MACC1 has activated this HGF/Met signaling pathway, tumor cells proliferate much faster, get rid of their ties within the cellular tissue, and eventually settle down as metastasis at various sights throughout the body far from the original tumor.

High MACC1 Levels - Higher Risk for Metastasis

The researchers discovered the MACC1 gene by comparing tissue from healthy persons with tissue from 103 patients with colon cancer between 20 to 88 years of age. Sixty (60) cancer patients had no metastasis at the time they underwent surgery.

Of these 60 patients, 37 had no metastasis five years after surgery and treatment. These patients were shown to have had low levels of MACC1 when first diagnosed with colon cancer. In contrast, 23 patients had developed metastasis in the course of five years after surgery. Researchers detected high levels of MACC1 in their colon cancer tissue. Thus, patients with high MACC1 levels have a much higher risk for developing metastasis than patients with a MACC1 gene that is not very active.

The researchers are convinced that MACC1 will enable physicians to decide if a patient needs a more intense therapy or if a less aggressive treatment is sufficient. "The expression analysis of MACC1 in the original tumor tissue will probably contribute to individualize and optimize colon cancer therapy", they assume.

Now the MDC and Charite researchers and their colleagues want to find out if the MACC1 gene also allows for a more precise prediction about the outcome of lung cancer, breast cancer, and stomach cancer.

MACC1, a newly identified key regulator of HGF-Met signaling, predicts colon cancer metastasis

Ulrike Stein1,2, Wolfgang Walther1,2, Franziska Alt1,2, Holger Schwabe2, Janice Smith1, Iduna Fichtner1, Walter Birchmeier1, Peter M. Schlag 1,2

1Max Delbrück Center for Molecular Medicine, Robert RössleStrasse 10, 13125 Berlin, Germany 2Department of Surgery and Surgical Oncology, Robert Rössle Cancer Hospital Charité University Medicine Berlin, Lindenberger Weg 80, 13125 Berlin, Germany

Foundation under Public Law
Directors:
Prof. Walter Birchmeier, PhD., Cornelia Lanz

Member of the Hermann von Helmholtz Association of National Research Centres

Further information: http://www.cancer.gov/cancertopics/types/colon-and-rectal

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Cellular Reprogramming: Science's Breakthrough Of The Year

In its annual list of the year's top ten scientific breakthroughs, the journal Science has given top honors to research that produced "made-to-order" cell lines by reprogramming cells from ill patients. These cell lines, and the techniques for producing them, offer long-sought tools for understanding -- and hopefully someday curing -- difficult-to-study diseases such as Parkinson's disease and type 1 diabetes.

Science and its publisher, AAAS, the nonprofit science society, now salute cellular reprogramming as the Breakthrough of the Year and recognize nine more of the year's most significant scientific accomplishments. The top ten list appears in a special feature in the journal's 19 December 2008 issue.

"When Science's writers and editors set out to pick this year's biggest advances, we looked for research that answers major questions about how the universe works and that paves the way for future discoveries. Our top choice, cellular reprogramming, opened a new field of biology almost overnight and holds out hope of life-saving medical advances," said deputy news editor Robert Coontz.

Two years ago, in experiments with mice, researchers showed that they could wipe out a cell's developmental "memory" by inserting just four genes. Once returned to its pristine, embryonic state, the cell could then be coaxed to become an altogether different type of cell.

This year, scientists built on this work with spectacular results. Two research teams took cells from patients suffering from a variety of diseases and reprogrammed them into stem cells. Many of these diseases are difficult or impossible to study with animal models, making the need for human cell lines to study even more acute.

The transformed cells grow and divide in the laboratory, unlike most adult cells, which don't survive in culture conditions. The cells could then be induced to assume new identities, including those cell types most affected by the diseases afflicting the patients who had donated the initial cells.

A third research team skipped the embryonic state altogether and, working with mouse cells, turned one type of mature pancreas cells, called exocrine cells, directly into another type, called beta cells.

The new cell lines will be major tools for understanding how diseases arise and develop, and they may also prove useful in screens for potential drugs. Eventually, if scientists can master cellular reprogramming so that it's more finely controlled, efficient and safe, patients may someday be treated with healthy versions of their own cells.

The other nine scientific achievements of 2008 follow. Except for the first runner-up, the direct detection of extrasolar planets, they are in no particular order.

Exoplanets - Seeing Is Believing: For the first time this year, astronomers directly observed planets orbiting other stars, using special telescope techniques to distinguish the planets' faint light from the stars' bright glare.

Expanding the Catalog of Cancer Genes: By sequencing genes from various cancer cells, including pancreatic cancer and glioblastoma, two of the deadliest cancers, researchers turned up dozens of mutations that remove the brakes on cell division and send the cell down the path to cancer.

New Mystery Materials: High-temperature superconductors are materials that carry electricity without resistance at inexplicably high temperatures. In 2008, researchers created a stir by discovering a whole second family of high-temperature superconductors, consisting of iron compounds instead of copper-and-oxygen-compounds.

Watching Proteins at Work: Biochemists encountered major surprises this year as they watched proteins bind to their targets, switch a cell's metabolic state and contribute to a tissue's properties.

Toward Renewable Energy on Demand: This year, researchers found a promising new tool for storing excess electricity generated from part-time sources like wind and solar power, on industrial scale. A cobalt-phosphorus catalyst that's relatively easy to come by can use electricity to split water to free its hydrogen, which can in turn be fed into fuel cells to produce electricity again.

The Video Embryo: In 2008, researchers observed in unprecedented detail the dance of cells in a developing embryo, recording and analyzing movies that trace the movements of the roughly 16,000 cells that make up the zebrafish embryo by the end of its first day of development.

"Good" Fat, Illuminated: In a study that may offer new approaches to treating obesity, scientists discovered that they could morph "good" brown fat, which burns "bad" white fat to generate heat for the body, into muscle and vice versa.

Calculating the Weight of the World: Physicists now have the calculations in hand to show that the standard model -- which describes most of the visible universe's particles and their interactions -- accurately predicts how much mass protons and neutrons have.

Faster, Cheaper Genome Sequencing: Researchers reported a flurry of genome sequences this year - from woolly mammoths to human cancer patients - aided by a variety of sequencing technologies that are much speedier and cheaper than the ones used to sequence the first human genome.

Areas to Watch: Science's predictions for hot science topics in 2009 include plants genomics, the elusive Higgs boson, speciation genes, ocean acidification, and neuroscience in court.

The special news features also looks at how the financial meltdown - the Breakdown of the Year - affected scientific research, and the major scientific collaborations getting off the ground in Europe.

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