Navigation Links
A New Target for Cancer Therapy-Integrin Alpha7 Molecule

Mutations in the cell adhesion molecule known as integrin alpha 7 (integrin 7) lead to unchecked tumor cell proliferation and aggressive cancer, 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 alpha7 represents an important new target for cancer therapy and prevention.

Integrin alpha7 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 alpha7 expression is associated with clinical relapse of human cancers. They also investigated whether integrin alpha7 has tumor suppressor activity.

To determine whether mutations in integrin alpha7 contribute to cancer, Dr. Luo and his collaborators sequenced the integrin alpha7 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 alpha7 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 alpha7 mutations also were associated with a significant increa se in the recurrence of cancer among patients. Nine of 13 prostate cancer patients with integrin alpha7 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 alpha7 mutations versus only one recurrence of cancer among 16 patients without such mutations.

To examine the effect of alterations in the level of integrin alpha7 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 alpha7 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 alpha7 expression formed fewer and smaller colonies. When the investigators decreased the level of integrin alpha7 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 alpha7 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 alpha7 in metastasis by examining the relationship between the level of integrin alpha7 expression and cell migration by increasing the expression of normal integrin alpha7 in three cell lines. The migration rate was significantly reduced in all of the cells compared to those in which the expression of integrin alpha7 remained deficient, suggesting that the level of normal integrin alpha7 expression is inversely associated with tumor cell migration.

Finally, to investigate whether normal integrin alpha7 possesses tumor suppressor activity, the researchers im planted human cancer cells into immune deficient mice. Some mice received tumor cells in which levels of integrin alpha7 were increased, others received tumor cells in which the levels of normal integrin alpha7 were decreased.

Six weeks after mice were implanted with cancer cells in which levels of normal integrin alpha7 were deficient, they had tumors with an average volume about four times as large as mice with implanted cancer cells in which normal integrin alpha7 levels were increased. Similarly, the researchers found no visible metastasis in mice with tumors in which levels of normal integrin alpha7 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 alpha7 and in four of the 12 mice with another type of tumor deficient in normal integrin alpha7. Furthermore, the six-week survival of mice bearing tumors with increased levels of normal integrin alpha7 was higher than that of mice bearing tumors in which normal integrin alpha7 had not been experimentally increased. Thus, increasing the level of normal integrin alpha7 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 alpha7 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 alpha7 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 alpha7 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 alpha7 levels in tumor cells in vi vo, 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.


'"/>




Related medicine news :

1. Target for obesity treatment
2. Gel Offers A More Targeted Approach
3. In Search Of A New Drug To Target Cholesterol
4. In Search Of A New Drug To Target Cholesterol
5. Target of diabetes type 1 identified
6. Gene Target For Tuberculosis Identified
7. New Vaccine Targeted At Effective Treatment Against Tuberculosis
8. Novel Technique For Targeting Small-Cell Lung Cancer
9. Ovarian Cancer Presents ‘Target Symptoms’ Six Months Before Diagnosi
10. Doctors, Pharma Companies Targeted By CBI Raids
11. Research Targets treatment for dementia and brain injuries
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/26/2016)... ... May 26, 2016 , ... Georgia State University ... specialty academic programs. , Answering to the increasing demand for curricular specializations, the ... law, and environmental and land use law. ,  , “The demand for lawyers ...
(Date:5/26/2016)... ... May 26, 2016 , ... The Woodlands at John Knox ... new model of care for living and healing, celebrated its grand opening, today. The ... a Real Home provided by Empowered Staff. , “This is an incredibly fulfilling time ...
(Date:5/26/2016)... ... May 26, 2016 , ... MadgeTech will be showcasing its line of ... Warner, New Hampshire at the MadgeTech headquarters. With products sold in more than 100 ... government agencies, including NASA. , In 2012, NASA strategically set up 17 RHTemp101A ...
(Date:5/26/2016)... ... ... An April Gallup survey found rising health care costs to be the top ... Living (SHSL) may not share those same worries thanks to a new bundled ... while holding the line on increasing their contributions, including premiums, deductibles and the portions ...
(Date:5/26/2016)... ... May 26, 2016 , ... Leadership ... solutions, today announced the organization has earned its ISO 13485 certification, indicating the ... compliant with all rules and policies associated with ISO quality standard 13485. ...
Breaking Medicine News(10 mins):
(Date:5/27/2016)... , May 27, 2016 ... the Dario™ Diabetes Management Tool, today announced that the Company,s ... the Marcum MicroCap Conference being held June 1-2 in ... Invitational, being held June 7-9 in Los Angeles, ... will discuss recent corporate and operational milestones, including the U.S. ...
(Date:5/27/2016)... Amarantus BioScience Holdings, Inc. (OTCQX: AMBS), ... Neurology and Orphan Diseases, today announced that President & CEO ... conferences: SeeThru Equity MicroCap Conference   ... City , NY When: Tuesday, May 31 st ... Where: Grand Hyatt Hotel, 109 East 42 nd ...
(Date:5/26/2016)... TARE (Transarterial Radio-embolization) Using ... and Overall Decreased Use of Hospital Resource ... specialist healthcare company, has today announced the publication ... of ISPOR (International Society for Pharmacoeconomics and Outcomes ... using yttrium-90 glass microspheres is associated with cost ...
Breaking Medicine Technology: