title: Colorectal cancer-derived microvesicles modulate differentiation of human monocytes to macrophages.
abstract: BACKGROUND
  Tumour-derived microvesicles (TMVs) are important players in tumour progression, modulating biological activity of immune cells e.g. lymphocytes, monocytes and macrophages. This phenomenon is particularly interesting in the progression of colon cancer, as macrophages in this type of tumour are relevant for the recovery processes. In the present study, the role of colon cancer cell-derived microvesicles in monocyte differentiation and activity profile (polarization) was investigated.
  
  
  METHODS
  Monocyte-derived macrophages (MDM) were differentiated in vitro in the presence of TMVs obtained from colon cancer: Caco-2, SW620, LoVo or SW480 cell lines and analysed according to their morphology and biological functions, as defined by cytokine secretion, reactive oxygen intermediate (ROI) production and cytotoxic activity against respective colon cancer cells.
  
  
  RESULTS
  Monocytes differentiated with TMVs exhibited morphological and phenotypical characteristics of macrophages. An early contact (beginning with the first day of the in vitro culture) of monocytes with TMVs resulted in increased IL-10 secretion and only slightly elevated TNF release. Early, or prolonged contact resulted in low ROI production and low cytotoxicity against tumour cells. On the other hand, late contact of MDM with TMVs, stimulated MDM to significant TNF and IL-12 secretion, ROI production and enhanced cytotoxicity against tumour cells in vitro. In addition, differences in MDM response to TMVs from different cell lines were observed (according to cytokine secretion, ROI production and cytotoxicity against tumour cells in vitro). Biological activity, STATs phosphorylation and microRNA profiling of MDMs indicated differences in their polarization/activation status which may suggest mixed polarization type M1/M2 with the predominance of proinflammatory cells after late contact with TMVs.
  
  
  CONCLUSIONS
  Macrophage activity (polarization status) may be regulated by contact with not only tumour cells but also with TMVs. Their final polarization status depends on the contact time, and probably on the vesicle "cargo", as signified by the distinct impact of TMVs which enabled the switching of MDM maturation to regulatory macrophages.
authors.affiliation: Department of Clinical Immunology, Institute of Peadiatrics, Medical College, Jagiellonian University, 265 Wielicka str., 30-663, Cracow, Poland. mibaj@cyf-kr.edu.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Baj-Krzyworzeka
authors.affiliation: Department of Clinical Immunology, Institute of Peadiatrics, Medical College, Jagiellonian University, 265 Wielicka str., 30-663, Cracow, Poland. mimytar@cyf-kr.edu.pl.
authors.forename: Bożenna
authors.initials: B
authors.lastname: Mytar
authors.affiliation: Department of Clinical Immunology, Institute of Peadiatrics, Medical College, Jagiellonian University, 265 Wielicka str., 30-663, Cracow, Poland. rafal.szatanek@uj.edu.pl.
authors.forename: Rafał
authors.initials: R
authors.lastname: Szatanek
authors.affiliation: Division of Molecular Biology and Clinical Genetics, Department of Internal Medicine, Medical College, Jagiellonian University, Cracow, Poland. marcin.surmiak@uj.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Surmiak
authors.affiliation: Department of Clinical Immunology, Institute of Peadiatrics, Medical College, Jagiellonian University, 265 Wielicka str., 30-663, Cracow, Poland. kazimierz.weglarczyk@uj.edu.pl.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Węglarczyk
authors.affiliation: Department of Clinical Immunology, Institute of Peadiatrics, Medical College, Jagiellonian University, 265 Wielicka str., 30-663, Cracow, Poland. mibaran@cyf-kr.edu.pl.
authors.forename: Jarek
authors.initials: J
authors.lastname: Baran
authors.affiliation: Department of Clinical Immunology, Institute of Peadiatrics, Medical College, Jagiellonian University, 265 Wielicka str., 30-663, Cracow, Poland. misiedla@cyf-kr.edu.pl.
authors.forename: Maciej
authors.initials: M
authors.lastname: Siedlar
mesh_terms: D015153:Blotting, Western; D016923:Cell Death; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D048430:Cell Shape; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: D016207:Cytokines; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor
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