title: Diverse in vivo effects of soluble and membrane-bound M-CSF on tumor-associated macrophages in lymphoma xenograft model.
abstract: Macrophage colony-stimulating factor (M-CSF) is an important cytokine for monocyte/macrophage lineage. Secretory M-CSF (sM-CSF) and membrane-bound M-CSF (mM-CSF) are two major alternative splicing isoforms. The functional diversity of these isoforms in the activation of tumor-associated macrophages (TAMs), especially in lymphoma microenvironment, has not been documented. Here, we studied the effects of M-CSF isoforms on TAMs in xenograft mouse model. More infiltrating TAMs were detected in microenvironment with mM-CSF and sM-CSF. TAMs could be divided into three subpopulations based on their expression of CD206 and Ly6C. While sM-CSF had greater potential to recruit and induce differentiation of TAMs and TAM subpopulations, mM-CSF had greater potential to induce proliferation of TAMs and TAM subpopulations. Though both isoforms educated TAMs and TAM subpopulations to M2-like macrophages, mM-CSF and sM-CSF induced different spectrums of phenotype-associated genes in TAMs and TAM subpopulations. These results suggested the diverse effects of M-CSF isoforms on the activation of TAMs and TAM subpopulations in lymphoma microenvironments.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Liao
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.|Center for Stem Cell Medicine, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Guoguang
authors.initials: G
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D000066670:Cell Plasticity / Q000187:drug effects; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology; D037181:Lectins, C-Type / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008262:Macrophage Activation; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility; D014162:Transfection; D059016:Tumor Microenvironment
chemical_list: D000950:Antigens, Ly; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor
keywords: TAMs; lymphoma; mM-CSF; sM-CSF; subpopulation