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!
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy