title: Endostatin inhibits the growth and migration of 4T1 mouse breast cancer cells by skewing macrophage polarity toward the M1 phenotype.
abstract: The phenotypic diversity of tumor-associated macrophages (TAMs) increases with tumor development. One of the hallmarks of malignancy is the polarization of TAMs from a pro-immune (M1) phenotype to an immunosuppressive (M2) phenotype. However, the molecular basis of this process is still unclear. Endostatin is a powerful inhibitor of angiogenesis capable of suppressing tumor growth and metastasis. Here, we demonstrate that endostatin induces RAW264.7 cell polarization toward the M1 phenotype in vitro. Endostatin has no effect on TAM numbers in vivo, but results in an increased proportion of F4/80(+)Nos2(+) cells and a decreased proportion of F4/80(+)CD206(+) cells. Overexpression of endostatin in RAW264.7 cells resulted in a decrease in the phosphorylation of STAT3, an increase in expression of vascular endothelial growth factor A and placental growth factor, and an increase in the phosphorylation of STAT1, IκBα and p65 proteins compared with controls. These results indicate that endostatin regulates macrophage polarization, promoting the M1 phenotype by targeting NF-κB and STAT signaling.
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, School of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, School of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, 250013, Shandong, People's Republic of China.
authors.forename: Junlian
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, School of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, School of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Lianqin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, School of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Center, School of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China. lyang@jlu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D043169:Endostatins / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D010641:Phenotype; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D043169:Endostatins
keywords: 4T1; Endostatin; Macrophage polarization; TAM