title: The function of cancer-shed gangliosides in macrophage phenotype: involvement with angiogenesis.
abstract: Tumor-derived gangliosides in the tumor microenvironment are involved in the malignant progression of cancer. However, the molecular mechanisms underlying the effects of gangliosides shed from tumors on macrophage phenotype remain unknown. Here, we showed that ganglioside GM1 highly induced the activity and expression of arginase-1 (Arg-1), a major M2 macrophage marker, compared to various gangliosides in bone marrow-derived macrophages (BMDM), peritoneal macrophages and Raw264.7 macrophage cells. We found that GM1 bound to macrophage mannose receptor (MMR/CD206) and common gamma chain (γc). In addition, GM1 increased Arg-1 expression through CD206 and γc-mediated activation of Janus kinase 3 (JAK3) and signal transducer and activator of transcription- 6 (STAT-6). Interestingly, GM1-stimulated macrophages secreted monocyte chemoattractant protein-1 (MCP-1/CCL2) through a CD206/γc/STAT6-mediated signaling pathway and induced angiogenesis. Moreover, the angiogenic effect of GM1-treated macrophages was diminished by RS102895, an MCP-1 receptor (CCR2) antagonist. From these results we suggest that tumor-shed ganglioside is a secretory factor regulating the phenotype of macrophages and consequently enhancing angiogenesis.
authors.affiliation: Korean Medical Research Center for Healthy Aging and Yangsan, Gyeongsangnam-do, Republic of Korea.|School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Chung
authors.affiliation: Korean Medical Research Center for Healthy Aging and Yangsan, Gyeongsangnam-do, Republic of Korea.|School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Korean Medical Research Center for Healthy Aging and Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Mi-Ju
authors.initials: MJ
authors.lastname: Park
authors.affiliation: Korean Medical Research Center for Healthy Aging and Yangsan, Gyeongsangnam-do, Republic of Korea.|School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Choi
authors.affiliation: Department of Food Science and Technology, Keimyung University, Daegu, Republic of Korea.
authors.forename: Syng-Ook
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Clinical Pathology, TaeKyeung University, Gyeongsan, Gyeongsangbuk-do, Republic of Korea.
authors.forename: Keuk-Jun
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Kyunggi-do, Republic of Korea.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Changwan
authors.initials: C
authors.lastname: Hong
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Kyun-Ha
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Korean Medical Research Center for Healthy Aging and Yangsan, Gyeongsangnam-do, Republic of Korea.|School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Myungsoo
authors.initials: M
authors.lastname: Joo
authors.affiliation: Korean Medical Research Center for Healthy Aging and Yangsan, Gyeongsangnam-do, Republic of Korea.|School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Ki-Tae
authors.initials: KT
authors.lastname: Ha
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007142:Immunoglobulin gamma-Chains / Q000378:metabolism; D053616:Janus Kinase 3 / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D011956:Receptors, Cell Surface / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D059016:Tumor Microenvironment
chemical_list: D007142:Immunoglobulin gamma-Chains; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D005677:G(M1) Ganglioside; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D001119:Arginase
keywords: angiogenesis; ganglioside; macrophage mannose receptor; monocyte chemoattractant protein-1; tumor-associated macrophage