title: The non-inflammatory role of C1q during Her2/neu-driven mammary carcinogenesis.
abstract: There is an ever increasing amount of evidence to support the hypothesis that complement C1q, the first component of the classical complement pathway, is involved in the regulation of cancer growth, in addition to its role in fighting infections. It has been demonstrated that C1q is expressed in the microenvironment of various types of human tumors, including breast adenocarcinomas. This study compares carcinogenesis progression in C1q deficient (neuT-C1KO) and C1q competent neuT mice in order to investigate the role of C1q in mammary carcinogenesis. Significantly accelerated autochthonous neu+carcinoma progression was paralleled by accelerated spontaneous lung metastases occurrence in C1q deficient mice. Surprisingly, this effect was not caused by differences in the tumor-infiltrating cells or in the activation of the complement classical pathway, since neuT-C1KO mice did not display a reduction in C3 fragment deposition at the tumor site. By contrast, a significant higher number of intratumor blood vessels and a decrease in the activation of the tumor suppressor WW domain containing oxidoreductase (WWOX) were observed in tumors from neuT-C1KO as compare with neuT mice. In parallel, an increase in Her2/neu expression was observed on the membrane of tumor cells. Taken together, our findings suggest that C1q plays a direct role both on halting tumor angiogenesis and on inducing apoptosis in mammary cancer cells by coordinating the signal transduction pathways linked to WWOX and, furthermore, highlight the role of C1q in mammary tumor immune surveillance regardless of complement system activation.
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bandini
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Macagno
authors.affiliation: Department of Medicine Science, Center of Excellence on Aging and Translational Medicine (CeSI-Met), G. d'Annunzio University of Chieti Pescara , Italy.
authors.forename: Albana
authors.initials: A
authors.lastname: Hysi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lanzardo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Conti
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Amanda
authors.initials: A
authors.lastname: Bello
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Riccardo
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ruiu
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Irene Fiore
authors.initials: IF
authors.lastname: Merighi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
authors.affiliation: Department of Medicine Science, Center of Excellence on Aging and Translational Medicine (CeSI-Met), G. d'Annunzio University of Chieti Pescara , Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Iezzi
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Quaglino
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Torino , Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
keywords: C1q; Complement; ErbB2; Her2/neu; genetically engineered mice; immunosurveillance; mammary cancer