C1q secreted in the tumour microenvironment promotes tumour growth in the absence of complement activation

We have recently shown that locally secreted C1q is involved in trophoblast invasion of decidua during pregnancy (Agostinis et al., J. Immunol. 2010;185;4420–4429). Since this physiologic process resembles to some extent tumor progression, we sought to investigate if C1q plays a similar role in tumor development and progression. Immunohistochemical analysis of several solid tumours including colon, prostate, lung and breast cancer and melanoma revealed the presence of C1q that was localized on the vascular endothelium and also distributed in the stroma in the absence of C4. To investigate the in vivo role of C1q in tumour development, 6/8 week old female WT and C1q−/− C57BL/6 mice received an intramuscular injection of 0.5×105 B16/F10 melanoma cells. The tumour mass measured daily for 2 weeks was significantly reduced in C1q−/− mice compared with WT animals and the survival of complement deficient mice was significantly prolonged. Interestingly, the tumor growth of B16 melanoma syngeneic model established in C3 and C5−/− mice and the survival rate of tumorbearing C3 and C5 deficient mice were not significantly different from those observed in WT mice. C1q was detected by immunofluorescence analysis on the vessel endothelium and in the stroma of the tumor mass in WT mice in the absence of C4 and C3. The vessel density both inside the tumor mass and in the peritumoral area evaluated by CD34 staining was similar in WT and C1q−/− animals and no difference was observed in the percentage of cell types of tumour infiltrating leucocytes examined by FACS analysis in the two groups of mice. In vitro experiments were also performed to analyse the mechanism of C1q-mediated tumor growth. C1q was found to promote adhesion and migration of melonoma cells, but failed to induce cell proliferation. In conclusion, our data suggest that C1q present in the tumour microenvironment may contribute to tumor growth via a mechanism independent on complement activation.