Mouse studies suggest that blocking aid from white blood cells and stem cells could keep tumors contained
Working with mice, Johns Hopkins researchers report they have identified chemical signals that certain breast cancers use to recruit two types of normal cells needed for the cancers' spread. A description of the findings appears in the online early May edition of the Proceedings of the National Academy of Sciences.
"Blocking one of these cell-recruiting signals in a mouse's tumor made it much less likely to metastasize or spread," says Gregg Semenza, M.D., Ph.D., a professor and director of the Vascular Biology Program in the Johns Hopkins University School of Medicine's Institute for Cell Engineering.
"If a drug can be found that safely blocks the same signal in humans, it could be a very useful addition to current breast cancer treatment — particularly for patients with chemotherapy-resistant tumors."
Semenza's research group studies a chemical signal called hypoxia-inducible factor 1 (HIF-1), which cells release to help them cope with low-oxygen conditions. Earlier, the group determined that HIF-1 helps breast tumor cells survive the low-oxygen conditions in which they often live, and spread to other parts of the body such as the lungs. "In breast cancer, it's not the original tumor that kills patients, but the metastases," says Semenza.
Also in a previous study, Semenza's group found that HIF-1 induced adult stem cells called mesenchymal stem cells release a signal to nearby breast cancer cells, which made them more likely to spread. The researchers suspected this communication might run both ways and that the stem cells' presence might also help the cancer to recruit the host animal's white blood cells. Breast cancers need the support of several types of host cells in order to metastasize, including mesenchymal stem cells and one type of white blood cell, Semenza notes.
Studying tumor cells grown in a dish, Semenza's team used chemicals that blocked the functions of various proteins to map a web of signals flying among breast cancer cells, menenchymal stem cells and white blood cells. One positive feedback loop brought mesenchymal stem cells close in to the breast cancer cells. A separate loop of signals between the stem cells and cancer cells caused the cancer cells to release a chemical "beacon" that drew in white blood cells. The concentrations of all the signals in the web were increased by the presence of HIF-1 — and ultimately, by low-oxygen conditions.
The team then used genetic engineering to reduce the levels of the cell-recruiting signals in breast cancer cells and implanted those cells into female mice. Compared with unaltered breast cancer cells, those with reduced recruiting power grew into similar-sized tumors, Semenza says, but were much less likely to spread.
All of the breast cancer cells used in the study were so-called triple-negative, meaning they lack receptors for estrogen, progesterone and human epidermal growth factor receptor 2, so they do not respond to therapies that target those receptors. In people, triple-negative breast cancers also tend to be more deadly than other breast cancers because they contain more HIF-1, Semenza says. "This study adds to the evidence that a HIF-1 inhibitor drug could be an effective addition to chemotherapy regimens, especially for triple-negative breast cancers," he says. Several potential drugs of this kind are now in the early stages of development, he notes.
Link to the paper: http://www.pnas.org/content/early/2014/05/01/1406655111.abstract
Other authors on this paper were Pallavi Chaturvedi, Daniele M. Gilkes and Naoharu Takano, all of the Johns Hopkins University School of Medicine.
Johns Hopkins Researchers Discover How Breast Cancer Spreads to Lung http://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_researchers_discover_how_breast_cancer_spreads_to_lung
Johns Hopkins Researchers Link Cell Division And Oxygen Levels http://www.hopkinsmedicine.org/news/media/releases/johns_hopkins_researchers_link_cell_division_and_oxygen_levels
Shawna Williams | Eurek Alert!
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses