Environmental and Genetic Activation of a Brain-Adipocyte BDNF/Leptin Axis Causes Cancer Remission and Inhibition
被引:287
作者:
Cao, Lei
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Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Cao, Lei
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Liu, Xianglan
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Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Liu, Xianglan
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Lin, En-Ju D.
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Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Lin, En-Ju D.
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Wang, Chuansong
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Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Wang, Chuansong
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Choi, Eugene Y.
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Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Choi, Eugene Y.
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Riban, Veronique
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Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Riban, Veronique
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Lin, Benjamin
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Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USAOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Lin, Benjamin
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During, Matthew J.
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机构:
Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
Ohio State Univ, Dept Neurosci & Neurol Surg, Columbus, OH 43210 USA
Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USA
Univ Auckland, Ctr Brain Res, Dept Mol Med & Pathol, Fac Med & Hlth Sci, Auckland 1023, New ZealandOhio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA
During, Matthew J.
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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
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.
机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Barb, Diana
Williams, Catherine J.
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Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Williams, Catherine J.
Neuwirth, Anke K.
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机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Neuwirth, Anke K.
Mantzoros, Christos S.
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机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
机构:
Rockefeller Univ, Howard Hughes Med Inst, Mol Neurooncol Lab, New York, NY 10021 USARockefeller Univ, Howard Hughes Med Inst, Mol Neurooncol Lab, New York, NY 10021 USA
Darnell, Robert B.
Posner, Jerome B.
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机构:Rockefeller Univ, Howard Hughes Med Inst, Mol Neurooncol Lab, New York, NY 10021 USA
机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Barb, Diana
Williams, Catherine J.
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h-index: 0
机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Williams, Catherine J.
Neuwirth, Anke K.
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h-index: 0
机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
Neuwirth, Anke K.
Mantzoros, Christos S.
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h-index: 0
机构:
Harvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USAHarvard Univ, Div Endocrinol Diabet & Metab, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
机构:
Rockefeller Univ, Howard Hughes Med Inst, Mol Neurooncol Lab, New York, NY 10021 USARockefeller Univ, Howard Hughes Med Inst, Mol Neurooncol Lab, New York, NY 10021 USA
Darnell, Robert B.
Posner, Jerome B.
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机构:Rockefeller Univ, Howard Hughes Med Inst, Mol Neurooncol Lab, New York, NY 10021 USA