"Melanoma is the most aggressive and metastatic form of skin cancer," said Gavin Robertson, professor of pharmacology, pathology, dermatology and surgery in the Penn State College of Medicine. "Therefore, identifying proteins and molecular mechanisms that regulate metastasis is important for developing drugs to treat this disease."
Metastasis is a complex process in which cancer cells detach from the primary tumor and migrate to other sites in the body by traveling through the lymphatic or blood circulatory systems. Researchers in the Foreman Foundation Melanoma Research Laboratory at Penn State developed a model to determine why the roughly one million tumor cells shed daily from a 1-gram melanoma tumor do not form more metastases in the lungs.
After intravenously injecting 1 million human melanoma cells in a mouse, Robertson and colleagues observed entrapment of many of these cells in the lung vessels. Within 24 hours, however, few cells were still present in the lungs.
"In this study, we show that entrapped, circulating melanoma cells can use a person's own immune cells -- specifically a type of white blood cell called neutrophils -- to control lung metastasis development," Robertson said. After injecting the mice with neutrophils an hour following the melanoma cell injection, cancer cell retention was increased in the lung by about three times.
Melanoma cells produce and secrete high levels of a protein called IL-8, which is used to attract neutrophils.
"For patients, this is important because a therapy preventing circulating melanoma cells from secreting IL-8 would have the potential to decrease lung metastasis development by about 50 percent by disrupting interaction of the cancer cells with neutrophils," Robertson said. "Metastases form by proteins on the melanoma and neutrophils interacting and forming physical connections. These connections promote anchoring of the melanoma cells to the lung vessel walls, enabling the cancer cells to migrate through the wall to form lung metastases."
Decreasing the secretion of IL-8 limits the interaction of melanoma cells with neutrophils, dropping the number of melanoma cells retained in the lungs by about half.
Findings were published in the journal Cancer Research. Funding for the study was provided by the National Institutes of Health and the Foreman Foundation for Melanoma Research.Other authors on the report are Penn State graduate students Sung Jin Huh of the Department of Pharmacology and Shile Liang of the Department of Bioengineering, assistant professor Arati Sharma of the Department of Pharmacology, and professor Cheng Dong, who all are members of the Melanoma Therapeutics Program at Penn State.
Matt Solovey | EurekAlert!
A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich
New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
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”...
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...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
17.02.2017 | Medical Engineering
17.02.2017 | Medical Engineering
17.02.2017 | Health and Medicine