A “vicious cycle” produces mucus that protects uterine and pancreatic cancer cells and promotes their proliferation, according to researchers at Rice University. The researchers offer hope for a therapeutic solution.
The presence of rosiglitazone may mitigate the mucus-producing cycle that protects uterine and pancreatic cancer cells and promotes metastasis, say researchers at Rice University. Normal cells produce MUC1, a glycoprotein that forms mucus, necessary to protect healthy cells. But in cancer cells, aberrant cell signaling allows EGFRs and MUC1 stimulate each other, allowing mucus to cover and protect the entire cell. “P” indicates phosphorylation, a step in the activation of EGFR required for increasing mucus levels. (Graphic by Brian Engel/Rice University)
They found that protein receptors on the surface of cancer cells go into overdrive to stimulate the production of MUC1, a glycoprotein that forms mucin, aka mucus. It covers the exposed tips of the elongated epithelial cells that coat internal organs like lungs, stomachs and intestines to protect them from infection.
But when associated with cancer cells, these slippery agents do their jobs too well. They cover the cells completely, help them metastasize and protect them from attack by chemotherapy and the immune system.
Details of the new work led by biochemist Daniel Carson, dean of Rice’s Wiess School of Natural Sciences, appear in the Journal of Cellular Biochemistry.
In the paper, Carson, lead author Neeraja Dharmaraj, a postdoctoral researcher, and graduate student Brian Engel described MUC1 overexpression as particularly insidious not only for the way it protects tumor cells and promotes metastasis, but also because the cells create a feedback loop in which epidermal growth factor receptors (EGFR) and MUC1 interact to promote each other.
Carson described EGFR as a powerful transmembrane protein that stimulates normal cell growth, proliferation and differentiation. “What hadn’t been considered is whether this activated receptor might actually promote the expression of MUC1, which would then further elevate the levels of EGFR and create this vicious cycle.
“That’s the question we asked, and the answer is ‘yes,’” he said.
Carson compared mucus to Teflon. “Things don’t stick to it easily, which is normally what you want. It’s a primary barrier that keeps nasty stuff like pathogenic bacteria and viruses from getting into your cells,” he said.
But cancer cells “subvert systems and find ways to get out of control,” he said. “They auto-activate EGFR by making their own growth factor ligands, for example, or mutating the receptor so it doesn’t require the ligand anymore. It’s always on.”
Mucin proteins can then cover entire surface of a cell. “That lets (the cell) detach and move away from the site of a primary tumor,” while still preventing contact with immune system cells and cytotoxins that could otherwise kill cancer cells, Carson said.
Hope comes in the form of a controversial drug, rosiglitazone, in the thiazolidinedione class of medications used in diabetes treatment, he said. The drug is suspected of causing heart problems over long-term use by diabetes patients. But tests on cancer cell lines at Rice found that it effectively attenuates the activation of EGFR and reduces MUC1 expression. That could provide a way to weaken the mucus shield.
“Chronic use of rosiglitazone can produce heart problems in a subset of patients, but if you’re dying of pancreatic cancer, you’re not worried about the long term,” Carson said. ”If you can reduce mucin levels in just a few days by using these drugs, they might make cancer cells easier to kill by established methods.”
He said more work is required to see if rosiglitazone or some variant is suitable for trials. “We think it’s best to understand all the effects,” he said. “That might give us a rational way to modify these compounds, to avoid unwanted side effects and focus on what we want them to do.”
Carson is the Schlumberger Chair of Advanced Studies and Research and a professor of biochemistry and cell biology with a joint appointment in the Department of Biochemistry and Molecular Biology at the University of Texas MD Anderson Cancer Center. He also is Rice’s vice provost for strategic partnerships.
The National Institutes of Health and Rice University supported the research.
David Ruth | EurekAlert!
'Flamenco dancing' molecule could lead to better-protecting sunscreen
18.10.2019 | University of Warwick
Synthetic cells make long-distance calls
17.10.2019 | Rice University
A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)
It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...
Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.
The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...
Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.
Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...
A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.
The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...
Superconductivity has fascinated scientists for many years since it offers the potential to revolutionize current technologies. Materials only become superconductors - meaning that electrons can travel in them with no resistance - at very low temperatures. These days, this unique zero resistance superconductivity is commonly found in a number of technologies, such as magnetic resonance imaging (MRI).
Future technologies, however, will harness the total synchrony of electronic behavior in superconductors - a property called the phase. There is currently a...
02.10.2019 | Event News
02.10.2019 | Event News
19.09.2019 | Event News
18.10.2019 | Physics and Astronomy
18.10.2019 | Materials Sciences
18.10.2019 | Life Sciences