Integrin á7 belongs to a major class of cell membrane proteins that play a role in the attachment of a cell to the extracellular matrix (ECM), which is the material that holds cells within a particular type of tissue together. Integrins also help cells attach to one another and are involved in transmitting chemical signals between cells and the ECM.
In this study, the researchers, led by Jianhua Luo, M.D., Ph.D., associate professor in the division of molecular and cellular pathology, University of Pittsburgh School of Medicine, examined whether this gene is mutated in specimens of various human cancers as well as whether the level of integrin á7 expression is associated with clinical relapse of human cancers. They also investigated whether integrin á7 has tumor suppressor activity.
To determine whether mutations in integrin á7 contribute to cancer, Dr. Luo and his collaborators sequenced the integrin á7 genes from 66 human cancer specimens and cell lines representing a number of different kinds of cancer, including cancer of the prostate, liver, brain (glioblastoma) and muscle (leiomyosarcoma).
They found mutations in the integrin á7 gene, particularly those that resulted in an abnormally shortened protein product, or truncation, in 16 of 28 prostate cancers. They also found truncation-inducing mutations in five of 24 liver cancer samples, five of six glioblastomas, and one of four leiomyosarcomas.
Integrin á7 mutations also were associated with a significant increase in the recurrence of cancer among patients. Nine of 13 prostate cancer patients with integrin á7 mutations experienced a recurrence of their cancer after radical prostatectomy versus only one of eight prostate cancer patients without such mutations. There were five recurrences among eight hepatocellular carcinoma patients with integrin á7 mutations versus only one recurrence of cancer among 16 patients without such mutations.
To examine the effect of alterations in the level of integrin á7 on tumor formation, the researchers assessed the ability of cancer cells to form colonies in a standard growth medium after increasing or decreasing the level of normal integrin á7 in the cell lines. In this experiment, control cancer cells formed large colonies with up to 100 cells each. Cancer cells with normal levels of integrin á7 expression formed fewer and smaller colonies. When the investigators decreased the level of integrin á7 in two cancer cells lines using siRNAs, or silencing RNAs, both cell lines formed more colonies and grew better than corresponding control cell lines.
“When we increased levels of normal integrin á7 in cancer cells, they grew at a much slower rate. This suggests that this protein is a fairly potent tumor suppressor,” said Dr. Luo.
Dr. Luo and his coworkers then investigated the role of integrin á7 in metastasis by examining the relationship between the level of integrin á7 expression and cell migration by increasing the expression of normal integrin á7 in three cell lines. The migration rate was significantly reduced in all of the cells compared to those in which the expression of integrin á7 remained deficient, suggesting that the level of normal integrin á7 expression is inversely associated with tumor cell migration.
Finally, to investigate whether normal integrin á7 possesses tumor suppressor activity, the researchers implanted human cancer cells into immune deficient mice. Some mice received tumor cells in which levels of integrin á7 were increased, others received tumor cells in which the levels of normal integrin á7 were decreased. Six weeks after mice were implanted with cancer cells in which levels of normal integrin á7 were deficient, they had tumors with an average volume about four times as large as mice with implanted cancer cells in which normal integrin á7 levels were increased. Similarly, the researchers found no visible metastasis in mice with tumors in which levels of normal integrin á7 had been increased. On the other hand, they did find evidence of metastasis in three of 12 mice with one type of tumor deficient in normal integrin á7 and in four of the 12 mice with another type of tumor deficient in normal integrin á7. Furthermore, the six-week survival of mice bearing tumors with increased levels of normal integrin á7 was higher than that of mice bearing tumors in which normal integrin á7 had not been experimentally increased. Thus, increasing the level of normal integrin á7 in tumors was associated with decreased tumor growth and metastasis in this animal model.
According to Dr. Luo and his coworkers, these findings suggest that not only is integrin á7 an important tumor suppressor, but it is potentially a critical new target for cancer treatment.
“Our study shows rather definitively that when we experimentally decreased the level of integrin á7 protein or the protein was naturally mutated in cells, those cells lost their inhibitory signals for both cell migration and proliferation. This suggests that the loss of integrin á7 activity may lead to unchecked tumor cell proliferation and a significantly increased risk of tumor metastasis. More importantly, it suggests that if we can somehow restore normal integrin á7 levels in tumor cells in vivo, we may be able to reduce the risk of them spreading to other sites, which would be a significant achievement in cancer therapy,” explained Dr. Luo.
Jim Swyers | EurekAlert!
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering