title: C1q acts in the tumour microenvironment as a cancer-promoting factor independently of complement activation.
abstract: Complement C1q is the activator of the classical pathway. However, it is now recognized that C1q can exert functions unrelated to complement activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. Compared with wild-type (WT) or C3- or C5-deficient mice, C1q-deficient (C1qa(-/-)) mice bearing a syngeneic B16 melanoma exhibit a slower tumour growth and prolonged survival. This effect is not attributable to differences in the tumour-infiltrating immune cells. Tumours developing in WT mice display early deposition of C1q, higher vascular density and an increase in the number of lung metastases compared with C1qa(-/-) mice. Bone marrow (BM) chimeras between C1qa(-/-) and WT mice identify non-BM-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings support a role for locally synthesized C1q in promoting tumour growth.
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bulla
authors.affiliation: Department of Human Pathology, University of Palermo, Palermo 90127, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Rami
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, London W12 0NN, UK.
authors.forename: Guang Sheng
authors.initials: GS
authors.lastname: Ling
authors.affiliation: Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico Burlo Garofolo, Trieste 34137, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Agostinis
authors.affiliation: Department of Human Pathology, University of Palermo, Palermo 90127, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Guarnotta
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Zorzet
authors.affiliation: Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Durigutto
authors.affiliation: Centre for Complement and Inflammation Research, Department of Medicine, Imperial College, London W12 0NN, UK.
authors.forename: Marina
authors.initials: M
authors.lastname: Botto
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Auxologico Italiano, Milan 20145, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003167:Complement Activation / Q000502:physiology*; D015922:Complement C1q / Q000235:genetics / Q000378:metabolism*; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009369:Neoplasms / Q000378:metabolism*
chemical_list: D003176:Complement C3; D003182:Complement C5; D015922:Complement C1q
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