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.
authors.affiliation: Division of Immunology, Transplantation & Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute San Raffaele University, School of Medicine, Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cottone
authors.affiliation: Division of Immunology, Transplantation & Infectious Diseases, San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Capobianco
authors.affiliation: Division of Immunology, Transplantation & Infectious Diseases, San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Gualteroni
authors.affiliation: Division of Immunology, Transplantation & Infectious Diseases, San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Monno
authors.affiliation: Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milano, Italy; Medicine and Surgery Department, University of Milano Bicocca, Milano, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Raccagni
authors.affiliation: Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milano, Italy; IBFM, CNR, Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Valtorta
authors.affiliation: Department of Radiology and Preclinical Imaging Facility of the Experimental Imaging Center, San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Tamara
authors.initials: T
authors.lastname: Canu
authors.affiliation: San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute , Milano, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Di Tomaso
authors.affiliation: Vita-Salute San Raffaele University, School of Medicine, Milano, Italy; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Lombardo
authors.affiliation: Vita-Salute San Raffaele University, School of Medicine, Milano, Italy; Department of Radiology and Preclinical Imaging Facility of the Experimental Imaging Center, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Esposito
authors.affiliation: Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milano, Italy; Medicine and Surgery Department, University of Milano Bicocca, Milano, Italy.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
authors.affiliation: Vita-Salute San Raffaele University, School of Medicine, Milano, Italy; Department of Radiology and Preclinical Imaging Facility of the Experimental Imaging Center, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Alessandro Del
authors.initials: AD
authors.lastname: Maschio
authors.affiliation: Vita-Salute San Raffaele University, School of Medicine, Milano, Italy; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Naldini
authors.affiliation: Division of Immunology, Transplantation & Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute San Raffaele University, School of Medicine, Milano, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rovere-Querini
authors.affiliation: Vita-Salute San Raffaele University, School of Medicine, Milano, Italy; Division of Genetics & Cell Biology, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
authors.affiliation: Division of Immunology, Transplantation & Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy; Vita-Salute San Raffaele University, School of Medicine, Milano, Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
keywords: Alarmin; BoxA; DAMP; GFP; HMGB1; High Mobility Box 1; MC-38; ShRNA; damage-associated molecular pattern; green fluorescent protein; leukocytes; macrophages; murine colon adenocarcinoma cell line; peritoneal carcinomatosis; short hairpin RNA; vascularization