“Latest Stem Cells News”

December 4, 2009- Working with mice, scientists at Johns Hopkins publishing in the December issue of Neoplasia have shown that a protein made by a gene called “Twist” may be the proverbial red flag that can accurately distinguish stem cells that drive aggressive, metastatic breast cancer from other breast cancer cells.

Building on recent work suggesting that it is a relatively rare subgroup of stem cells in breast tumors that drives breast cancer, scientists have surmised that this subgroup of cells must have some very distinctive qualities and characteristics.

In experiments designed to identify those special qualities, the Hopkins team focused on the gene “Twist” (or TWIST1) – named for its winding shape – because of its known role as the producer of a so-called transcription factor, or protein that switches on or off other genes. Twist is an oncogene, one of many genes we are born with that have the potential to turn normal cells into malignant ones.

“Our experiments show that Twist is a driving force among a lot of other players in causing some forms of breast cancer,” says Venu Raman, Ph.D., associate professor of radiology and oncology, Johns Hopkins University School of Medicine. “The protein it makes is one of a growing collection of markers that, when present, flag a tumor cell as a breast cancer stem cell.”

Previous stem cell research identified a Twist-promoted process known as epithelial-to-mesenchymal transition, or EMT, as an important marker denoting the special subgroup of breast cancer stem cells. EMT essentially gets cells to detach from a primary tumor and metastasize. The new Hopkins research shows that the presence of Twist, along with changes in two other biomarkers – CD 24 and CD44 – even without EMT, announces the presence of this critical sub-group of stem cells.
“The conventional thinking is that the EMT is crucial for recognizing the breast cancer cell as stem cells, and the potential for metastasis, but our studies show that when Twist shows up in excess or even at all, it can work independently of EMT,” says Farhad Vesuna, Ph.D., an instructor of radiology in the Johns Hopkins University School of Medicine. “EMT is not mandatory for identifying a breast cancer stem cell.”

Working with human breast cancer cells transplanted into mice, all of which had the oncogene Twist, the scientists tagged cell surface markers CD24 and CD44 with fluorescent chemicals. Following isolation of the subpopulation containing high CD44 and low CD24 by flow cytometry, they counted 20 of these putative breast cancer stem cells. They then injected these cells into the breast tissue of 12 mice. All developed cancerous tumors.

“Normally, it takes approximately a million cells to grow a xenograft, or transplanted tumor,” Vesuna says. “And here we’re talking just 20 cells. There is something about these cells – something different compared to the whole bulk of the tumor cell – that makes them potent. That’s the acid test – if you can take a very small number of purified “stem cells” and grow a cancerous tumor, this means you have a pure population.”

Previously, the team showed that 65 percent of aggressive breast cancers have more Twist compared to lower-grade breast cancers, and that Twist-expressing cells are more resistant to radiation.
Twist is what scientists refer to as an oncogene, one that if expressed when and where it’s not supposed to be expressed, causes oncogenesis or cancer because the molecules and pathways that once regulated it and kept it in check are gone.

This finding – that Twist is integral to the breast cancer stem cell phenotype – has fundamental implications for early detection, treatment and prevention, Raman says. Some cancer treatments may kill ordinary tumor cells while sparing the rare cancer stem cell population, sabotaging treatment efforts. More effective cancer therapies likely require drugs that kill this important stem cell population.

This study was supported by the Maryland Stem Cell Research Foundation.

In addition to Vesuna and Raman, authors of the paper include Ala Lisok and Brian Kimble, also of Johns Hopkins.

fonte http://www.hopkinsmedicine.org/Press_releases/2009/12_04_09.html

The Pisa University Hospital has become part of the international network of hematopoietic stem cell transplant facilities (meaning they produce various blood components). The hospital was recently accredited by the Italian registry of bone marrow donors, which is part of the international network.

Pisa has become an important center for bone marrow collection for all potential donors in northwestern Italy.
On 20 April 2009, the first donation was carried out for a patient at the Udine University Hospital, and a second donation is being organized for a patient being treated at the Montpellier Hospital (France).

The hospital in Pisa received the prestigious recognition thanks to the positive results they have obtained over the past years in the hematology and oncology- hematology units.

Much to the dismay of patients and physicians, cancer stem cells — tiny powerhouses that generate and maintain tumor growth in many types of cancers — are relatively resistant to the ionizing radiation often used as therapy for these conditions. Part of the reason, say researchers at Stanford University School of Medicine, is the presence of a protective pathway meant to shield normal stem cells from DNA damage. When the researchers blocked this pathway, the cells became more susceptible to radiation.

“Our ultimate goal is to come up with a therapy that knocks out the cancer stem cells,” said Robert Cho, MD, a clinical instructor of pediatrics. “If you irradiate a tumor and kill a lot of it but leave the cancer stem cells behind, the tumor has the ability to grow back.” As a result, patients can relapse months or years after seemingly successful treatment.

Cho and radiation oncologist and post-doctoral fellow Maximilian Diehn, MD, PhD, are co-first authors of the research, which was published on Feb. 4 in Nature. They collaborated with scientists at Stanford and City of Hope National Medical Center to conduct the research. They studied breast epithelial stem cells from humans and mice to unravel why cancer stem cells are more resistant to radiation than other cancer cells.

“Since cancer stem cells appear to be responsible for driving and maintaining tumor growth in many tumors, it is critical to understand the mechanisms by which these cells resist commonly used therapies such as chemotherapy and radiotherapy,” said Diehn. “Ultimately, we hope to improve patient outcomes by developing therapeutic approaches that directly target cancer stem cells or that overcome their resistance mechanisms.”

The origin of cancer stem cells is still under debate. Some may arise from normal adult stem cells gone awry. Others may represent specialized cells from adult tissues that have acquired a stem-cell-like state through a series of mutations. What’s clear is that cancer stem cells can reconstitute an entire tumor cell population when transplanted into an immune-deficient animal, and destroying them is likely to be critical in order to stop the growth and spread of the disease.

Andreas Trumpp

Andreas Trumpp and his colleagues from the German Cancer Research Center have recently spoken about a “silent reserve” of stem cells, wondering what type of medical impact the discovery made in Heidelberg of “dormant stem cells” could have.

Usually, dormant bone marrow cells activate and multiply only in a crisis or emergency to react to serious cellular loss due to a virus or hemorrhage. When their work is done, they return to a dormant stage. This withdrawal phase keeps them protected from mutations, cellular toxins, and other dangerous substances, since the cells do not divide and are not subject to modifications or various types of aggressions.

According to the Trumpp group’s discovery, the dormant reserve can even be recruited artificially using alpha interferon proteins, as reported in Nature magazine (10.1038/nature07815).
This is an important result for various reasons. Alpha interferon is the body’s response to viral attacks on cells. Its release can be an intense, sort of SOS for the cell.

Dalhousie Medical School cancer researcher Dr. Patrick Lee has proven that a common virus can infect and kill breast cancer stem cells. This breakthrough finding is published in the current issue of Molecular Therapy, the journal of the American Society of Gene Therapy.

It is only within the past few years that the scientific community has understood the full significance of cancer stem cells and the urgent need to find a means of eliminating them.

“Cancer stem cells are essentially mother cells,” explains Dr. Lee, Cameron Chair in Basic Cancer Research at Dalhousie Medical School. “They continuously produce new cancer cells, aggressively forming tumours even when there are only a few of them.”

Cancer stem cells are difficult to kill as they respond poorly to chemotherapy and radiation. As Dr. Lee notes, “You can kill all the regular cancer cells in a tumour, but as long as there are cancer stem cells present, disease will recur.”

The first operations have been successfully performed at Seriate Hospital (Bergamo) using autologous stem cell transplants to rebuild a part of the breast after removing a tumor. The technique used in the operation is known as ‘lipofilling’, which calls for some of the patient’s abdominal fat to be removed in a procedure similar to liposuction. The fat is then purified and manipulated in the laboratory to concentrate stem cells as much as possible, then they are transplanted into the portion of the breast that has been removed to eliminate the cancer.