Macrophages modulate migration and invasion of human tongue squamous cell carcinoma

Autor: Pia Nyberg, Paula Pesonen, Lars Uhlin-Hansen, Marilena Vered, Sini Nurmenniemi, Tuula Salo, Kaisa Päkkilä, Emma Pirilä, Elias Sundquist, Dan Dayan, Virve Pääkkönen, Otto Väyrynen
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Pathology
medicine.medical_treatment
lcsh:Medicine
Cell Communication
Mice
0302 clinical medicine
Cell Movement
Epidermal growth factor
skin and connective tissue diseases
lcsh:Science
Cells
Cultured
0303 health sciences
Multidisciplinary
NF-kappa B
Cell migration
Endocytosis
VDP::Medical disciplines: 700::Basic medical
dental and veterinary science disciplines: 710
Tongue Neoplasms
3. Good health
Cytokine
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
Cytokines
Heterografts
medicine.symptom
Research Article
medicine.medical_specialty
Inflammation
Biology
03 medical and health sciences
Cell Line
Tumor
Carcinoma
medicine
Animals
Humans
Neoplasm Invasiveness
Efferocytosis
030304 developmental biology
Tumor microenvironment
Macrophages
lcsh:R
VDP::Medisinske Fag: 700::Basale medisinske
odontologiske og veterinærmedisinske fag: 710
medicine.disease
Coculture Techniques
Rats
Disease Models
Animal
Cell culture
Cancer research
lcsh:Q
Biomarkers
Zdroj: PLoS ONE, Vol 10, Iss 3, p e0120895 (2015)
PLoS ONE
ISSN: 1932-6203
Popis: Oral 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.
Databáze: OpenAIRE
Externí odkaz: