Navigation Links
Study reveals how normal cells fuel tumor growth
Date:12/21/2011

Research summary:

  • The study shows how normal cells in tumors can enhance the growth of the tumor's cancer cells after losing an important tumor suppressor gene called Pten.

  • The findings suggest a new strategy for treating breast cancer by interrupting signals between normal cells and cancer cells in tumors.

    COLUMBUS, Ohio A new study published in the journal Nature Cell Biology has discovered how normal cells in tumors can fuel tumor growth.

    Led by researchers at the Ohio State University Comprehensive Cancer Center Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC James), the study examines what happens when normal cells called fibroblasts in mouse mammary tumors lose an important tumor-suppressor gene called Pten (pronounced "P ten").

    The findings suggest new strategies for controlling tumor growth by developing drugs that disrupt the communication between tumor cells and the normal cells within the tumor. They also provide insight into the mechanisms that control the co-evolution of cancer cells and surrounding normal cells in tumors, and they demonstrate how the Pten gene normally suppresses cancer development, the researchers say.

    "Our study is the first to define a specific pathway in tumor fibroblasts that reprograms gene activity and the behavior of multiple cell types in the tumor microenvironment, including tumor cells themselves," says co-principal investigator Dr. Michael Ostrowski, professor and chair of molecular and cellular biochemistry.

    "Along with increasing basic knowledge about how tumors grow and spread, these findings have direct translational implications for the treatment of breast-cancer patients," says Ostrowski, who is a member of the OSUCCC James Molecular Biology and Cancer Genetics program.

    The researchers found that Pten regulates a molecule called microRNA-320 (miR-320), and that the loss of Pten leads to a dramatic drop in levels of that molecule in a tumor fibroblast. With little miR-320 around, levels of a protein called ETS2 (pronounced Ets-two) rise in the fibroblast.

    Finally, the abundance of ETS2 activates a number of genes that cause the fibroblast to secrete more than 50 factors that stimulate the proliferation and invasiveness of nearby cancer cells. It also causes the reprogramming of other fibroblasts in the tumor and throughout the mammary gland.

    "The cancer field has long focused solely on targeting tumor cells for therapy," says co-principal investigator Gustavo Leone, associate professor of molecular virology, immunology and medical genetics. "Our work suggests that modulation of a few key molecules such as miR-320 in noncancer cells in the tumor microenvironment might be sufficient to impede the most malignant properties of tumor cells."

    Ostrowski, Leone and their colleagues began this study by examining human invasive breast tumors from 126 patients for microRNA changes after PTEN loss.

    Key technical findings include the following:

    • Using mouse models, they found that miR-320 levels and ETS2 levels were inversely correlated in human breast-tumor tissue, suggesting that Pten and miR-320 work together to block ETS2 function and suppress tumor growth.

    • miR-320 in mammary fibroblasts influences the behavior of multiple cell types, making it a critical molecule for suppressing epithelial tumors.

    • miR-320 functions as a regulatory switch in normal fibroblasts that operates to inhibit the secretion of more than 50 tumor-promoting factors (i.e., a tumor-promoting secretome). In doing so, it blocks the expression of genes in other cell types in the tumor microenvironment and suppresses tumor-cell growth and invasiveness.

  • Overall, loss of Pten in tumor fibroblasts results in downregulation of miR-320 and release of the secretome factors. This causes the genetic reprogramming of neighboring endothelial and epithelial cells of the mammary gland, inciting profound changes in these cells that are typical of malignant tumors.

    "Remarkably, the molecular signature of the miR-320 secretome could distinguish normal breast tissue from tumor tissue, and it predicted the outcome in breast-cancer patients," says Leone, who is also a member of the OSUCCC James Molecular Biology and Cancer Genetics program. "This underscores the potential clinical importance of the Pten-miR-320 regulatory pathway on human breast cancer."


    '/>"/>

  • Contact: Darrell E. Ward
    Darrell.Ward@osumc.edu
    614-293-3737
    Ohio State University Medical Center
    Source:Eurekalert

    Related medicine news :

    1. Despite Treatment, Employees with Depression Generate Higher Absentee Costs, According to Thomson Reuters Study
    2. American Council on Exercise (ACE) Study Reveals Kettlebells Provide Powerful Workout in Short Amount of Time
    3. TV drama can be more persuasive than news program, study finds
    4. Study carried out into biological risks of eating reptiles
    5. Neuroimaging study may pave way for effective Alzheimers treatments
    6. Study finds racial gaps continue in heart disease awareness
    7. Luth Researchs IndicatorEDG(TM) Study Finds Americans Hopes of Achieving Their Dreams Are Fading
    8. First blinded study of venous insufficiency prevalence in MS shows promising results
    9. Soothing infants with food focus of childhood obesity study
    10. People with anxiety disorder less able to regulate response to negative emotions, study shows
    11. American Heart Association Rapid Access Journal Report: Study Finds Racial Gaps Continue in Heart Disease Awareness, Low Knowledge of Heart Attack Warning Signs Among Women
    Post Your Comments:
    *Name:
    *Comment:
    *Email:
    (Date:6/26/2016)... (PRWEB) , ... June 26, 2016 , ... PawPaws ... a new product that was developed to enhance the health of felines. The formula ... , The two main herbs in the PawPaws Cat Kidney Support Supplement ...
    (Date:6/25/2016)... D.C. (PRWEB) , ... June 25, 2016 , ... ... discuss health policy issues and applications at AcademyHealth’s Annual Research Meeting June 26-28, ... their work on several important health care topics including advance care planning, healthcare ...
    (Date:6/25/2016)... ... June 25, 2016 , ... "With 30 hand-drawn hand ... project," said Christina Austin - CEO of Pixel Film Studios. , ProHand Cartoon’s ... within Final Cut Pro X . Simply select a ProHand generator and drag ...
    (Date:6/25/2016)... ... June 25, 2016 , ... Dr. Calvin Johnson has ... he has implemented orthobiologic procedures as a method for treating his patients. The ... first doctors to perform the treatment. Orthobiologics are substances that orthopaedic surgeons use ...
    (Date:6/24/2016)... Angeles, CA (PRWEB) , ... June 24, 2016 , ... ... surgery procedures that most people are unfamiliar with. The article goes on to state ... procedures, but also many of these less common operations such as calf and cheek ...
    Breaking Medicine News(10 mins):
    (Date:6/24/2016)... CAMBRIDGE, Mass. , June 24, 2016 /PRNewswire/ ... the Spaulding Rehabilitation Network,s Dean Center for ... of Physical Medicine and Rehabilitation, MIT Hacking Medicine, ... Center for Innovation, today announced the five finalists ... Hackathon for Lyme disease.  More than 100 scientists, ...
    (Date:6/24/2016)... Dehaier Medical Systems Ltd. (NASDAQ: DHRM ) ... medical devices and wearable sleep respiratory products in ... with Hongyuan Supply Chain Management Co., Ltd. (hereinafter referred ... to develop Dehaier,s new Internet medical technology business. ... Hongyuan Supply Chain,s sales platform to reach Dehaier,s dealers ...
    (Date:6/24/2016)... June 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... innovative inhaled drugs, announced today that it was added ... reconstituted its comprehensive set of U.S. and global ... is an important milestone for Pulmatrix," said Chief Executive ... awareness of our progress in developing drugs for crucial ...
    Breaking Medicine Technology: