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Oncogene-Driven Intrinsic Inflammation Induces Leukocyte Production of Tumor Necrosis Factor That Critically Contributes to Mammary Carcinogenesis

  1. Author:
    Sangaletti, S.
    Tripodo, C.
    Ratti, C.
    Piconese, S.
    Porcasi, R.
    Salcedo, R.
    Trinchieri, G.
    Colombo, M. P.
    Chiodoni, C.

  2. Author Address

    [Sangaletti, Sabina; Ratti, Chiara; Piconese, Silvia; Colombo, Mario P.; Chiodoni, Claudia] Fdn IRCCS Ist Nazl Tumori, Mol Immunol Unit, Dept Expt Oncol & Mol Med, I-20133 Milan, Italy. [Tripodo, Claudio; Porcasi, Rossana] Univ Palermo, Dept Human Pathol, Palermo, Italy. [Salcedo, Rosalba; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD USA.;Colombo, MP, Fdn IRCCS Ist Nazl Tumori, Mol Immunol Unit, Dept Expt Oncol & Mol Med, Via Venezian 1, I-20133 Milan, Italy.;mario.colombo@istitutotumori.mi.it
    1. Year: 2010
    2. Date: Oct
  2. Journal: Cancer Research
    1. 70
    2. 20
    3. Pages: 7764-7775
  4. Type of Article: Article
  5. ISSN: 0008-5472
  1. Abstract:

    Oncogene activation promotes an intrinsic inflammatory pathway that is crucial for cancer development. Here, we have investigated the actual effect of the inflammatory cytokine tumor necrosis factor (TNF) on the natural history of spontaneous mammary cancer in the HER2/neuT (NeuT) transgenic mouse model. Bone marrow transplantation from TNF knockout mice into NeuT recipients significantly impaired tumor growth, indicating that the source of TNF fostering tumor development was of bone marrow origin. We show that the absence of leukocyte-derived TNF disarranged the tumor vasculature, which lacked pericyte coverage and structural integrity, leading to diffuse vascular hemorrhage and stromal necrosis. In addition, tumor-associated Tie2-expressing monocytes were reduced and cytokine expression skewed from Th2 to Th1 type. Treatment of NeuT mice with anti-TNF antibody partially phenocopied the antitumor effect of TNF-deficient bone marrow cell transplantation, providing a strong preclinical background and rationale for the introduction of TNF antagonists in the treatment of human breast cancer, including basal-like samples for which consolidated targeted therapies do not exist. Cancer Res; 70(20); 7764-75. (C) 2010 AACR.

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External Sources

  1. View Full Text
  2. DOI: 10.1158/0008-5472.can-10-0471
  3. View record in Web of Science®
  4. WOS: 000282879900005

Library Notes

  1. Fiscal Year: FY2010-2011
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