Environmental and Genetic Activation of a Brain-Adipocyte BDNF/Leptin Axis Causes Cancer Remission and Inhibition

被引:287
作者
Cao, Lei [1 ,2 ,3 ,4 ]
Liu, Xianglan [1 ,2 ,3 ]
Lin, En-Ju D. [1 ,2 ,3 ]
Wang, Chuansong [1 ,2 ,3 ]
Choi, Eugene Y. [1 ,2 ,3 ]
Riban, Veronique [1 ,2 ,3 ]
Lin, Benjamin [4 ]
During, Matthew J. [1 ,2 ,3 ,4 ,5 ]
机构
[1] Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
[2] Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
[3] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
[4] Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USA
[5] Univ Auckland, Ctr Brain Res, Dept Mol Med & Pathol, Fac Med & Hlth Sci, Auckland 1023, New Zealand
基金
美国国家卫生研究院;
关键词
NEUROTROPHIC FACTOR; STRESS; LEPTIN; EXERCISE; OBESITY; BDNF; HYPOTHALAMUS; ADAPTATION; PLASTICITY; ENRICHMENT;
D O I
10.1016/j.cell.2010.05.029
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cancer is influenced by its microenvironment, yet broader, environmental effects also play a role but remain poorly defined. We report here that mice living in an enriched housing environment show reduced tumor growth and increased remission. We found this effect in melanoma and colon cancer models, and that it was not caused by physical activity alone. Serum from animals held in an enriched environment (EE) inhibited cancer proliferation in vitro and was markedly lower in leptin. Hypothalamic brain-derived neurotrophic factor (BDNF) was selectively upregulated by EE, and its genetic overexpression reduced tumor burden, whereas BDNF knockdown blocked the effect of EE. Mechanistically, we show that hypothalamic BDNF downregulated leptin production in adipocytes via sympathoneural beta-adrenergic signaling. These results suggest that genetic or environmental activation of this BDNF/leptin axis may have therapeutic significance for cancer.
引用
收藏
页码:52 / 64
页数:13
相关论文
共 49 条
  • [1] GROWTH-FACTORS AND CANCER
    AARONSON, SA
    [J]. SCIENCE, 1991, 254 (5035) : 1146 - 1153
  • [2] Adiponectin in relation to malignancies: a review of existing basic research and clinical evidenced
    Barb, Diana
    Williams, Catherine J.
    Neuwirth, Anke K.
    Mantzoros, Christos S.
    [J]. AMERICAN JOURNAL OF CLINICAL NUTRITION, 2007, 86 (03) : 858S - 866S
  • [3] Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex
    Bariohay, B
    Lebrun, B
    Moyse, E
    Jean, A
    [J]. ENDOCRINOLOGY, 2005, 146 (12) : 5612 - 5620
  • [4] Brain-adipose tissue neural crosstalk
    Bartness, Timothy J.
    Song, C. Kay
    [J]. PHYSIOLOGY & BEHAVIOR, 2007, 91 (04) : 343 - 351
  • [5] Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity
    Benaroya-Milshtein, N
    Hollander, N
    Apter, A
    Kukulansky, T
    Raz, N
    Wilf, A
    Yaniv, I
    Pick, CG
    [J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 20 (05) : 1341 - 1347
  • [6] Obesity promotes melanoma tumor growth Role of leptin
    Brandon, Elizabeth L.
    Gu, Jian-Wei
    Cantwell, Lauren
    He, Zhi
    Wallace, Gray
    Hall, John E.
    [J]. CANCER BIOLOGY & THERAPY, 2009, 8 (19) : 1871 - 1879
  • [7] VEGF links hippocampal activity with neurogenesis, learning and memory
    Cao, L
    Jiao, XY
    Zuzga, DS
    Liu, YH
    Fong, DM
    Young, D
    During, MJ
    [J]. NATURE GENETICS, 2004, 36 (08) : 827 - 835
  • [8] Molecular therapy of obesity and diabetes by a physiological autoregulatory approach
    Cao, Lei
    Lin, En-Ju D.
    Cahill, Michael C.
    Wang, Chuansong
    Liu, Xianglan
    During, Matthew J.
    [J]. NATURE MEDICINE, 2009, 15 (04) : 447 - 454
  • [9] Leptin Signaling in Breast Cancer: An Overview
    Cirillo, Donatella
    Rachiglio, Anna Maria
    la Montagna, Raffaele
    Giordano, Antonio
    Normanno, Nicola
    [J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2008, 105 (04) : 956 - 964
  • [10] Paraneoplastic syndromes affecting the nervous system
    Darnell, Robert B.
    Posner, Jerome B.
    [J]. SEMINARS IN ONCOLOGY, 2006, 33 (03) : 270 - 298