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dc.contributor.authorPirilä, Emma
dc.contributor.authorVäyrynen, Otto
dc.contributor.authorSundquist, Elias
dc.contributor.authorPäkkilä, Kaisa
dc.contributor.authorNyberg, Pia
dc.contributor.authorNurmenniemi, Sini
dc.contributor.authorPääkkönen, Virve
dc.contributor.authorPesonen, Paula
dc.contributor.authorDayan, Dan
dc.contributor.authorVered, Marilena
dc.contributor.authorUhlin-Hansen, Lars
dc.contributor.authorSalo, Tuula
dc.date.accessioned2016-03-03T12:57:47Z
dc.date.available2016-03-03T12:57:47Z
dc.date.issued2015-03-26
dc.description.abstractOral tongue squamous cell carcinoma (OTSCC) has a high mortality rate and the incidence is rising worldwide. Despite advances in treatment, the disease lacks specific prognostic markers and treatment modality. The spreading of OTSCC is dependent on the tumor microenvironment and involves tumor-associated macrophages (TAMs). Although the presence of TAMs is associated with poor prognosis in OTSCC, the specific mechanisms underlying this are still unknown. The aim here was to investigate the effect of macrophages (Mfs) on HSC-3 tongue carcinoma cells and NF-kappaB activity. We polarized THP-1 cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type Mfs. We then investigated the effect of Mfs on HSC-3 cell migration and NF-kappaB activity, cytokine production and invasion using several different in vitro migration models, a human 3D tissue invasion model, antibody arrays, confocal microscopy, immunohistochemistry and a mouse invasion model. We found that in co-culture studies all types of Mfs fused with HSC-3 cells, a process which was partially due to efferocytosis. HSC-3 cells induced expression of epidermal growth factor and transforming growth factor-beta in co-cultures with M2 Mfs. Direct cell-cell contact between M2 Mfs and HSC-3 cells induced migration and invasion of HSC-3 cells while M1 Mfs reduced HSC-3 cell invasion. M2 Mfs had an excess of NF-kappaB p50 subunit and a lack of p65 subunits both in the presence and absence of HSC-3 cells, indicating dysregulation and pro-tumorigenic NF-kappaB activation. TAM-like cells were abundantly present in close vicinity to carcinoma cells in OTSCC patient samples. We conclude that M2 Mfs/TAMs have an important role in OTSCC regulating adhesion, migration, invasion and cytokine production of carcinoma cells favouring tumor growth. These results demonstrate that OTSCC patients could benefit from therapies targeting TAMs, polarizing TAM-like M2 Mfs to inflammatory macrophages and modulating NF-kappaB activity.en_US
dc.identifier.citationPLoS ONE 2015, 10(3): e0120895en_US
dc.identifier.cristinIDFRIDAID 1257336
dc.identifier.doi10.1371/journal.pone.0120895
dc.identifier.issn1932-6203
dc.identifier.urihttps://hdl.handle.net/10037/8650
dc.identifier.urnURN:NBN:no-uit_munin_8238
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleMacrophages modulate migration and invasion of human tongue squamous cell carcinomaen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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