Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find new contributor to aggressive cancers

08.06.2007
Mutations in the cell adhesion molecule known as integrin alpha 7 (integrin á7) lead to unchecked tumor cell proliferation and a significantly higher incidence in cancer spread, or metastasis, in several cancer cell lines, report researchers at the University of Pittsburgh School of Medicine in a study being published today in the Journal of the National Cancer Institute. These findings suggest that integrin á7 represents an important new target for cancer therapy and prevention.

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!
Further information:
http://www.upmc.edu

Further reports about: Integrin Luo colonies decreased deficient mutations recurrence tumor suppressor

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>