Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes.
This study was designed to determine the characteristics of tumour cell-derived microvesicles (TMV) and their interactions with human monocytes. TMV were shed spontaneously by three different human cancer cell lines but their release was significantly increased upon activation of the cells with phorbol 12-myristate 13-acetate (PMA). TMV showed the presence of several surface determinants of tumour cells, e.g. HLA class I, CD29, CD44v7/8, CD51, chemokine receptors (CCR6, CX3CR1), extracellular matrix metalloproteinase inducer (EMMPRIN), epithelial cell adhesion molecule (EpCAM), but their level of expression differed from that on cells they originated from. TMV also carried mRNA for growth factors: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-8 (IL-8) and surface determinants (CD44H). TMV were localized at the monocytes surface following their short exposure to TMV, while at later times intracellularly. TMV transferred CCR6 and CD44v7/8 to monocytes, exerted antiapoptotic effect on monocytes and activated AKT kinase (Protein Kinase B). Thus, TMV interact with monocytes, alter their immunophenotype and biological activity. This implicates the novel mechanism by which tumour infiltrating macrophages may be affected by tumour cells not only by a direct cell to cell contact, soluble factors but also by TMV.
Baj-Krzyworzeka
Monika
M
Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Wielicka 265 Str., 30-663 Cracow, Poland.
Szatanek
Rafał
R
Weglarczyk
Kazimierz
K
Baran
Jarosław
J
Urbanowicz
Barbara
B
Brański
Piotr
P
Ratajczak
Mariusz Z
MZ
Zembala
Marek
M
D000230:Adenocarcinoma / Q000276:immunology / Q000648:ultrastructure; D000951:Antigens, Neoplasm / Q000032:analysis / Q000276:immunology*; D017209:Apoptosis; D051926:Basigin / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000276:immunology / Q000648:ultrastructure; D002462:Cell Membrane / Q000276:immunology* / Q000648:ultrastructure; D002470:Cell Survival; D002633:Chemotaxis; D015179:Colorectal Neoplasms / Q000276:immunology / Q000648:ultrastructure; D020869:Gene Expression Profiling; D005805:Genes, MHC Class I; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D008175:Lung Neoplasms / Q000276:immunology / Q000648:ultrastructure; D008565:Membrane Proteins / Q000032:analysis / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000648:ultrastructure; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000648:ultrastructure; D010316:Particle Size; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000951:Antigens, Neoplasm; C497886:BSG protein, human; C497483:CD44 protein, human; D006680:HLA Antigens; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D051926:Basigin; D013755:Tetradecanoylphorbol Acetate