It is now recognized that C1q can exert functions unrelated to C activation. Here we show that C1q, but not C4, is expressed in the stroma and vascular endothelium of several human malignant tumours. We found that C1q-deficient (C1qa-/-) mice bearing a syngeneic B16 melanoma have a slower tumour growth and prolonged survival compared to wild-type (WT) or C3- or C5-deficient mice. This effect was not attributable to differences in the tumour infiltrating immune cells. Tumours developing in WT mice displayed early deposition of C1q, higher vascular density and increased number of lung metastases than those growing in C1qa-/- mice. Bone marrow chimeras between C1qa-/- and WT mice allowed the identification of non-bone marrow-derived cells as the main local source of C1q that can promote cancer cell adhesion, migration and proliferation. Together these findings strongly support a role for locally synthesized C1q in promoting tumour growth.
