Complement C1q induces the M2-polarization of tumor-associated macrophages in lung adenocarcinoma
Yuxiao Song, Yang Fu, Jun Wang, Jiazhuo Tang, Jiaxin Yin, Zhimin Zhang, Qibin Song, Bicheng Zhang
Abstract
Complement C1q induces the M2-polarization of tumor-associated macrophages in lung adenocarcinomaComplement C1q was proved to be able to regulate the polarization of macrophages to the anti-inflammatory phenotype (M2 polarized), acting as an anti-inflammation molecule independent of the classical complement pathway.A high level of C1q expression has been detected in the tumor microenvironment (TME) of diverse tumors, including non-small cell lung cancer, in which C1q could be considered a predictor of poor prognosis. 1Prominently, researchers have found that C1q was positively correlated with the M2 polarization of tumor-associated macrophages (TAMs) in mouse renal clear cell carcinoma and human osteosarcoma.M2-TAMs are significantly associated with immunosuppressive TME and poor prognosis in non-small cell lung cancer.Hence, we investigated the mutual effects between C1q and TAMs in lung adenocarcinoma.The findings of this study could be extracted as below: (i) The expression of C1qA was positively correlated with M2-TAMs in lung adenocarcinoma.(ii) M2-TAMs could express abundant C1q, and C1q in lung adenocarcinoma was mainly from TAMs, especially M2-TAMs.(iii) C1qA could promote the proportion of M2-TAMs.(iv) C1qA led to the reduced phosphorylation of JAK2, STAT1, and STAT5, but augmented the levels of p52, phospho-p65, and phospho-IkBa belonging to NF-kB pathway.(v) C1q promoted the growth of LLC xenograft.C1q consists of 18 polypeptide chains, including 6 C1qA, 6 C1qB, and 6 C1qC.Research has revealed that defects in the C1qA, C1qB, or C1qC genes were associated with disfunction of C1q, generating very similar responses.In this study, the bioinformatic analysis through Pearson and Spearman correlation test showed C1qA expression was positively correlated with M2-TAMs gene signatures in the lung adenocarcinoma database (Fig. 1A).Given the results of bioinformatic analysis, C1qA active protein was applied