Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis

Lucia Cottone, Annalisa Capobianco, Chiara Gualteroni, Antonella Monno, Isabella Raccagni, Silvia Valtorta, Tamara Canu, Tiziano Di Tomaso, Angelo 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

11 Citations (Scopus)

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
JournalOncoImmunology
DOIs
Publication statusAccepted/In press - Apr 30 2016

Fingerprint

Leukocytes
Carcinoma
Macrophages
Neoplasms
Colon
Growth
Clodronic Acid
Phagocytes
Pharmacology

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
  • Oncology
  • Immunology

Cite this

Cottone, L., Capobianco, A., Gualteroni, C., Monno, A., Raccagni, I., Valtorta, S., ... Manfredi, A. A. (Accepted/In press). Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis. OncoImmunology. https://doi.org/10.1080/2162402X.2015.1122860

Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis. / Cottone, Lucia; Capobianco, Annalisa; Gualteroni, Chiara; Monno, Antonella; Raccagni, Isabella; Valtorta, Silvia; Canu, Tamara; Tomaso, Tiziano Di; Lombardo, Angelo; Esposito, Antonio; Moresco, Rosa Maria; Maschio, Alessandro Del; Naldini, Luigi; Rovere-Querini, Patrizia; Bianchi, Marco E.; Manfredi, Angelo A.

In: OncoImmunology, 30.04.2016.

Research output: Contribution to journalArticle

Cottone L, Capobianco A, Gualteroni C, Monno A, Raccagni I, Valtorta S et al. Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis. OncoImmunology. 2016 Apr 30. https://doi.org/10.1080/2162402X.2015.1122860
Cottone, Lucia ; Capobianco, Annalisa ; Gualteroni, Chiara ; Monno, Antonella ; Raccagni, Isabella ; Valtorta, Silvia ; Canu, Tamara ; Tomaso, Tiziano Di ; Lombardo, Angelo ; Esposito, Antonio ; Moresco, Rosa Maria ; Maschio, Alessandro Del ; Naldini, Luigi ; Rovere-Querini, Patrizia ; Bianchi, Marco E. ; Manfredi, Angelo A. / Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis. In: OncoImmunology. 2016.
@article{5e6add2b6e124bfcb6124e554d5e9e2a,
title = "Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis",
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.",
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",
author = "Lucia Cottone and Annalisa Capobianco and Chiara Gualteroni and Antonella Monno and Isabella Raccagni and Silvia Valtorta and Tamara Canu and Tomaso, {Tiziano Di} and Angelo Lombardo and Antonio Esposito and Moresco, {Rosa Maria} and Maschio, {Alessandro Del} and Luigi Naldini and Patrizia Rovere-Querini and Bianchi, {Marco E.} and Manfredi, {Angelo A.}",
year = "2016",
month = "4",
day = "30",
doi = "10.1080/2162402X.2015.1122860",
language = "English",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Taylor and Francis Inc.",

}

TY - JOUR

T1 - Leukocytes recruited by tumor-derived HMGB1 sustain peritoneal carcinomatosis

AU - Cottone, Lucia

AU - Capobianco, Annalisa

AU - Gualteroni, Chiara

AU - Monno, Antonella

AU - Raccagni, Isabella

AU - Valtorta, Silvia

AU - Canu, Tamara

AU - Tomaso, Tiziano Di

AU - Lombardo, Angelo

AU - Esposito, Antonio

AU - Moresco, Rosa Maria

AU - Maschio, Alessandro Del

AU - Naldini, Luigi

AU - Rovere-Querini, Patrizia

AU - Bianchi, Marco E.

AU - Manfredi, Angelo A.

PY - 2016/4/30

Y1 - 2016/4/30

N2 - 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.

AB - 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.

KW - Alarmin

KW - BoxA

KW - damage-associated molecular pattern

KW - DAMP

KW - GFP

KW - green fluorescent protein

KW - High Mobility Box 1

KW - HMGB1

KW - leukocytes

KW - macrophages

KW - MC-38

KW - murine colon adenocarcinoma cell line

KW - peritoneal carcinomatosis

KW - short hairpin RNA

KW - ShRNA

KW - vascularization

UR - http://www.scopus.com/inward/record.url?scp=84965031845&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84965031845&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2015.1122860

DO - 10.1080/2162402X.2015.1122860

M3 - Article

AN - SCOPUS:84965031845

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

ER -