Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis

Lucia Cottone, Annalisa Capobianco, Chiara Gualteroni, Antonia Monno, Isabella Raccagni, Silvia Valtorta, Tamara Canu, Tiziano Di Tomaso, Angelo Leone Lombardo, Antonio Esposito, Rosa Maria Moresco, Alessandro Del Maschio, Luigi Naldini, Patrizia Rovere-Querini, Marco E. Bianchi, Angelo A. Manfredi

Research output: Contribution to journalArticle

Abstract

The factors that determine whether disseminated transformed cells in vivo yield neoplastic lesions have only been partially identified. We established an ad hoc model of peritoneal carcinomatosis by injecting colon carcinoma cells in mice. Tumor cells recruit inflammatory leukocytes, mostly macrophages, and generate neoplastic peritoneal lesions. Phagocyte depletion via clodronate treatment reduces neoplastic growth. Colon carcinoma cells release a prototypic damage-associated molecular pattern (DAMP)/alarmin, High Mobility Group Box1 (HMGB1), which attracts leukocytes. Exogenous HMGB1 accelerates leukocyte recruitment, macrophage infiltration, tumor growth and vascularization. Lentiviral-based HMGB1 knockdown or pharmacological interference with its extracellular impair macrophage recruitment and tumor growth. Our findings provide a preclinical proof of principle that strategies based on preventing HMGB1-driven recruitment of leukocytes could be used for treating peritoneal carcinomatosis.
Original languageEnglish
Article numbere1122860
Pages (from-to)-
JournalOncoImmunology
Volume5
Issue number5
DOIs
Publication statusPublished - May 3 2016

Keywords

  • Alarmin
  • BoxA
  • Damage-associated molecular pattern
  • DAMP
  • GFP
  • Green fluorescent protein
  • High mobility Box 1
  • HMGB1
  • Leukocytes
  • Macrophages
  • MC-38
  • Murine colon adenocarcinoma cell line
  • Peritoneal carcinomatosis
  • Short hairpin RNA
  • ShRNA
  • Vascularization

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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