Tumour-derived microvesicles modulate biological activity of human monocytes.
Tumour cells are shedding membrane fragments (tumour-derived microvesicles, TMV) that may interact with cells of immune system. Our previous observations indicated that TMV carry several surface determinants and mRNA of tumour cells and transfer some of them to monocytes. This study determined the effect of TMV on biological activity of human monocytes as the precursors of tumour infiltrating macrophages (TIM). It was found that TMV activated monocytes as shown by an increased HLA-DR expression, induced production of ROI (reactive oxygen intermediates) and of tumour necrosis factor (TNF), interleukin (IL)-10, IL-12p40 accumulation of mRNA and their secretion. Induction of TNF synthesis was CD44 dependent as blocking of CD44 on monocytes abolished its secretion. TMV-treated monocytes showed an increased antitumour activity as judged by enhanced cytotoxicity/cytostasis against tumour cells in vitro. Taken together, these results indicate that TMV significantly modulate biological activity of monocytes and thus mimic the effect of tumour cells on them. This may suggest that tumour cells interact with TIM not only via direct contact, soluble factors, but also 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
Zembala
Marek
M
D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism*; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism