Aino Salmiheimo1, Harri Mustonen1, Sanna Vainionpää1, Zhanlong Shen2, Esko Kemppainen1, Pauli Puolakkainen3, Hanna Seppänen1. 1. Department of Surgery, University of Helsinki, Helsinki University Hospital, Helsinki, Finland. 2. Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China. 3. Department of Surgery, University of Helsinki, Helsinki University Hospital, Helsinki, Finland. Electronic address: pauli.puolakkainen@hus.fi.
Abstract
OBJECTIVES: Tumour-associated macrophages participate in tumour development and progression. The aim of this study was to assess the interactions of pancreatic cancer cells and pro-inflammatory M1 and anti-inflammatory M2 macrophages, specifically their effect on pancreatic cancer cell migration and the changes in STAT-signalling. METHODS: Monocytes were isolated from healthy subjects and differentiated into macrophages with M-CSF. The macrophages were polarized towards M1 by IL-12 and towards M2 by IL-10. We studied also the effect of pan-JAK/STAT-inhibitor P6. Macrophage polarization and STAT and NFkB-activation in both MiaPaCa-2 and macrophages were assessed by flow cytometry. We recorded the effect of co-culture on migration rate of pancreatic cancer cells MiaPaCa-2. RESULTS: Macrophages increased the migration rate of pancreatic cancer cells. Co-culture activated STAT1, STAT3, STAT5, AKT, and NFkB in macrophages and STAT3 in MiaPaCa-2 cells. IL-12 polarized macrophages towards M1 and decreased the migration rate of pancreatic cancer cells in co-cultures as well as P6. IL-10 skewed macrophage polarization towards M2 and induced increase of pancreatic cancer cells in co-cultures. CONCLUSION: Co-culture with macrophages increased pancreatic cancer cell migration and activated STAT3. It is possible to activate and deactivate migration of pancreatic cancer cells trough macrophage polarization.
OBJECTIVES:Tumour-associated macrophages participate in tumour development and progression. The aim of this study was to assess the interactions of pancreatic cancer cells and pro-inflammatory M1 and anti-inflammatory M2 macrophages, specifically their effect on pancreatic cancer cell migration and the changes in STAT-signalling. METHODS: Monocytes were isolated from healthy subjects and differentiated into macrophages with M-CSF. The macrophages were polarized towards M1 by IL-12 and towards M2 by IL-10. We studied also the effect of pan-JAK/STAT-inhibitor P6. Macrophage polarization and STAT and NFkB-activation in both MiaPaCa-2 and macrophages were assessed by flow cytometry. We recorded the effect of co-culture on migration rate of pancreatic cancer cells MiaPaCa-2. RESULTS: Macrophages increased the migration rate of pancreatic cancer cells. Co-culture activated STAT1, STAT3, STAT5, AKT, and NFkB in macrophages and STAT3 in MiaPaCa-2 cells. IL-12 polarized macrophages towards M1 and decreased the migration rate of pancreatic cancer cells in co-cultures as well as P6. IL-10 skewed macrophage polarization towards M2 and induced increase of pancreatic cancer cells in co-cultures. CONCLUSION: Co-culture with macrophages increased pancreatic cancer cell migration and activated STAT3. It is possible to activate and deactivate migration of pancreatic cancer cells trough macrophage polarization.
Authors: Faraz Bishehsari; Lijuan Zhang; Usman Barlass; Nailliw Z Preite; Sanja Turturro; Matthew S Najor; Brandon B Shetuni; Janet P Zayas; Mahboobeh Mahdavinia; Abde M Abukhdeir; Ali Keshavarzian Journal: Int J Cancer Date: 2018-08-09 Impact factor: 7.396
Authors: Lara Campana; Philip J Starkey Lewis; Antonella Pellicoro; Rebecca L Aucott; Janet Man; Eoghan O'Duibhir; Sarah E Mok; Sofia Ferreira-Gonzalez; Eilidh Livingstone; Stephen N Greenhalgh; Katherine L Hull; Timothy J Kendall; Douglas Vernimmen; Neil C Henderson; Luke Boulter; Christopher D Gregory; Yi Feng; Stephen M Anderton; Stuart J Forbes; John P Iredale Journal: J Immunol Date: 2017-12-20 Impact factor: 5.422