Bulla Roberta, Tripodo Claudio, Rami Damiano, Ling Guang Sheng, Agostinis Chiara, Guarnotta Carla, Zorzet Sonia, Durigutto Paolo, Botto Marina, Tedesco Francesco
Department of Life Sciences, University of Trieste, Trieste 34127, Italy.
Department of Human Pathology, University of Palermo, Palermo 90127, Italy.
Nat Commun. 2016 Feb 1;7:10346. doi: 10.1038/ncomms10346.
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.
补体C1q是经典途径的激活剂。然而，现在人们认识到C1q可以发挥与补体激活无关的功能。在这里，我们表明C1q而非C4在几种人类恶性肿瘤的基质和血管内皮中表达。与野生型（WT）或C3或C5缺陷小鼠相比，携带同基因B16黑色素瘤的C1q缺陷（C1qa(-/-)）小鼠肿瘤生长较慢且生存期延长。这种效应并非归因于肿瘤浸润免疫细胞的差异。与C1qa(-/-)小鼠相比，WT小鼠中发生的肿瘤显示C1q早期沉积、更高的血管密度以及肺转移数量增加。C1qa(-/-)和WT小鼠之间的骨髓（BM）嵌合体确定非BM来源的细胞是C1q的主要局部来源，C1q可促进癌细胞的黏附、迁移和增殖。这些发现共同支持局部合成的C1q在促进肿瘤生长中发挥作用。
