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NIH study in mice uncovers pathway critical for UV-induced melanoma

Forums Cutaneous Melanoma Community NIH study in mice uncovers pathway critical for UV-induced melanoma

  • Post
    LynnLuc
    Participant

    I wanted to share this..it was released today…http://www.nih.gov/news/health/jan2011/nci-19.htm

     

    Embargoed for Release
    Wednesday, January 19, 2011
    1 p.m. EST

    Contact:
    NCI Office of Media Relations
    301-496-6641

    I wanted to share this..it was released today…http://www.nih.gov/news/health/jan2011/nci-19.htm

     

    Embargoed for Release
    Wednesday, January 19, 2011
    1 p.m. EST

    Contact:
    NCI Office of Media Relations
    301-496-6641

    NIH study in mice uncovers pathway critical for UV-induced melanoma

    Scientists have made an unanticipated discovery in mice that interferon-gamma, a type of protein primarily used by the immune system for intercellular communication, acts as a promoter for the deadly form of skin cancer known as melanoma. This finding resulted from a series of experiments designed to understand how solar ultraviolet (UV) radiation causes melanoma. The results of this study suggest that interferon-gamma, which has been thought to contribute to an innate defense system against cancer, under some circumstances may promote melanoma and incite the development of tumors. The work, led by researchers from the National Cancer Institute (NCI), part of the National Institutes of Health, appeared online in Nature, Jan. 19, 2011.

    Cutaneous melanoma is a highly aggressive and frequently drug-resistant cancer with rising incidence rates. The major environmental risk factor for melanoma is UV radiation exposure, usually from the sun, with the highest risk associated with intermittent burning doses, especially during childhood.

    Over the past 10 years, the researchers used genetically engineered mice first to prove, and then to try to understand, the connection between exposure to UV radiation and the initiation of melanoma. The current work was the latest attempt to define the molecular mechanisms of this cause and effect relationship. The results of this study offer the possibility that the inhibition of interferon-gamma immediately after sunburn might block the carcinogenic activation of the skin’s pigment-producing cells, known as melanocytes, making it a potentially effective preventive strategy against UV radiation-induced melanoma, according to the scientists.

    The key to the experiments, led by Glenn Merlino, Ph.D., Laboratory of Cancer Biology and Genetics, NCI, and research fellow and first author M. Raza Zaidi, Ph.D., was the development of a unique genetically engineered mouse in which the melanocytes were exclusively labeled with a green fluorescent protein. This fluorescent tag allowed visual tracking and specific purification of melanocytes from the mouse skin. For the first time this enabled researchers to evaluate the response of melanocytes to UV radiation exposure while residing in the natural skin environment of a living animal.

    The researchers observed that UV radiation doses equivalent to what would cause sunburn in human skin resulted in increased numbers and movement of melanocytes within the mouse skin. A detailed analysis of gene expression changes associated with this melanocyte activation revealed abnormal expression of a number of genes known to be responsive to interferon-gamma.

    When the function of interferon-gamma was inhibited at the time of UV radiation, the number of melanocytes and their movement remained normal, suggesting that interferon-gamma was responsible for the UV radiation-induced activation of the melanocytes.

    The source of interferon-gamma within the skin was determined to be macrophages — cells that normally protect against infection — that had infiltrated the skin after UV exposure. The pro-melanoma potential of these macrophages was revealed when they were found to enhance the growth of melanomas when transplanted under the skin of mice.

    This effect was abolished when interferon-gamma was blocked, corroborating its importance in promoting melanoma development. Moreover, when the scientists examined human melanoma tissue samples, they found interferon-gamma-producing macrophages in 70 percent of the tumors, supporting the idea that these macrophages can significantly contribute to the initiation and/or progression of human melanoma.

    "We anticipate that this discovery may change how interferons are used in the clinic as anticancer agents," said Merlino. "Our findings raise the possibility that targeting the interferon-gamma pathway may represent a novel, less toxic therapeutic alternative for effective treatment of malignant melanoma patients, who currently have poor cure rates."

    These studies were made possible through long-term collaborations with Edward De Fabo, Ph.D., and Frances Noonan, Ph.D., of George Washington University Medical Center, Washington, D.C.

    NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

    The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.


    Reference: Zaidi MR, et al., Interferon-gamma links ultraviolet radiation to melanomagenesis in mice, Nature, Jan. 27, 2010, DOI: 10.1038/nature09666.


     

     

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      EmilyandMike
      Participant

      Wow.  I am confused – does this mean alpha interferon could possibly be making things worse or is that different than gamma interferon?

      Trying to understand this paragraph:

      "We anticipate that this discovery may change how interferons are used in the clinic as anticancer agents," said Merlino. "Our findings raise the possibility that targeting the interferon-gamma pathway may represent a novel, less toxic therapeutic alternative for effective treatment of malignant melanoma patients, who currently have poor cure rates."

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      EmilyandMike
      Participant

      Wow.  I am confused – does this mean alpha interferon could possibly be making things worse or is that different than gamma interferon?

      Trying to understand this paragraph:

      "We anticipate that this discovery may change how interferons are used in the clinic as anticancer agents," said Merlino. "Our findings raise the possibility that targeting the interferon-gamma pathway may represent a novel, less toxic therapeutic alternative for effective treatment of malignant melanoma patients, who currently have poor cure rates."

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        KatyWI
        Participant

        I don't entirely understand the article, but interferon gamma definitlely is differnt from interferon alpha.

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        KatyWI
        Participant

        I don't entirely understand the article, but interferon gamma definitlely is differnt from interferon alpha.

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        LynnLuc
        Participant

        I have no personal experience using interferon or the difference in them…I bet Jimmy B would know. I found the article interesting because it could perhaps prevent a sunburn from damaging our skin to the extent that it would cause melanoma…where was this when I was a little girl with egg looking blisters on my shoulders!

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        LynnLuc
        Participant

        I have no personal experience using interferon or the difference in them…I bet Jimmy B would know. I found the article interesting because it could perhaps prevent a sunburn from damaging our skin to the extent that it would cause melanoma…where was this when I was a little girl with egg looking blisters on my shoulders!

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        EmilyandMike
        Participant

        I found another article that also explains the study (from Australia) and what was very scary was that this finding (I know we are just talking about mice at the moment) could "upend" the assumptions about Interferons and cancer. 

        http://www.abc.net.au/science/articles/2011/01/20/3117078.htm

         

        Upending assumptions about interferons

        The findings, reported in the journal Nature, could upend assumptions about the relationship between interferon proteins and cancer, say the study's researchers.

        Up to now, interferons were thought to impede the formation of cancer tumours. One in particular, interferon-alpha, has been widely used to treat melanoma, both as a first-line drug and an adjutant.

        Earlier research has raised doubts as to effectiveness of the treatment, which also has serious side effects.

        The highest recorded incidence of melanoma is in Australia, where the annual rates for women are 10 times the rate in Europe and more 20 times for men.

        The main risk factors are high exposure to the Sun and other UV sources such as sun-beds, along with genetic factors.

        The disease is far more common among people with a pale complexion, blue eyes, and red or fair hair.

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        EmilyandMike
        Participant

        I found another article that also explains the study (from Australia) and what was very scary was that this finding (I know we are just talking about mice at the moment) could "upend" the assumptions about Interferons and cancer. 

        http://www.abc.net.au/science/articles/2011/01/20/3117078.htm

         

        Upending assumptions about interferons

        The findings, reported in the journal Nature, could upend assumptions about the relationship between interferon proteins and cancer, say the study's researchers.

        Up to now, interferons were thought to impede the formation of cancer tumours. One in particular, interferon-alpha, has been widely used to treat melanoma, both as a first-line drug and an adjutant.

        Earlier research has raised doubts as to effectiveness of the treatment, which also has serious side effects.

        The highest recorded incidence of melanoma is in Australia, where the annual rates for women are 10 times the rate in Europe and more 20 times for men.

        The main risk factors are high exposure to the Sun and other UV sources such as sun-beds, along with genetic factors.

        The disease is far more common among people with a pale complexion, blue eyes, and red or fair hair.

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        LynnLuc
        Participant

        wow- I was thinking it could help prevent…not promote…so much information coming out! Sometimes it's overload!

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        LynnLuc
        Participant

        wow- I was thinking it could help prevent…not promote…so much information coming out! Sometimes it's overload!

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