Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion.
(2014) In Immunology and Cell Biology 92(6). p.543-552- Abstract
- At the time of diagnosis, almost 80% of pancreatic cancer patients present with new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic cancer are both associated with low-grade inflammation. Tumour-associated macrophages (TAMs) have a key role in cancer-related inflammation, immune escape, matrix remodelling and metastasis. In this study, the interplay between tumour cells and immune cells under the influence of different glucose levels was investigated. Human peripheral blood mononuclear cells were exposed in vitro to conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour-derived factors stimulated... (More)
- At the time of diagnosis, almost 80% of pancreatic cancer patients present with new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic cancer are both associated with low-grade inflammation. Tumour-associated macrophages (TAMs) have a key role in cancer-related inflammation, immune escape, matrix remodelling and metastasis. In this study, the interplay between tumour cells and immune cells under the influence of different glucose levels was investigated. Human peripheral blood mononuclear cells were exposed in vitro to conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour-derived factors stimulated differentiation of macrophages, with a mixed classical (M1-like) and alternatively activated (M2-like) phenotype polarisation (CD11c(+)CD206(+)). High-glucose conditions further enhanced the tumour-driven macrophage enrichment and associated interleukin (IL)-6 and IL-8 cytokine levels. In addition, hyperglycaemia enhanced the responsiveness of tumour-educated macrophages to lipopolysaccharide, with elevated cytokine secretion compared with normal glucose levels. Tumour-educated macrophages were found to promote pancreatic cancer cell invasion in vitro, which was significantly enhanced at high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype polarisation and reduced the tumour cell invasion at normal, but not high, glucose levels. In conclusion, this study demonstrates that pancreatic cancer cells stimulate differentiation of macrophages with pro-tumour properties that are further enhanced by hyperglycaemia. These findings highlight important crosstalk between tumour cells and TAMs in the local tumour microenvironment that may contribute to disease progression in pancreatic cancer patients with hyperglycaemia and T2D.Immunology and Cell Biology advance online publication, 25 March 2014; doi:10.1038/icb.2014.22. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4379794
- author
- Karnevi, Emelie LU ; Andersson, Roland LU and Rosendahl, Ann LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Immunology and Cell Biology
- volume
- 92
- issue
- 6
- pages
- 543 - 552
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:24662521
- wos:000338709600011
- scopus:84904054241
- pmid:24662521
- ISSN
- 1440-1711
- DOI
- 10.1038/icb.2014.22
- language
- English
- LU publication?
- yes
- id
- 928f6afa-1e21-4764-b9e4-e2e7dd358bcb (old id 4379794)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24662521?dopt=Abstract
- date added to LUP
- 2016-04-01 10:01:30
- date last changed
- 2022-02-02 05:38:04
@article{928f6afa-1e21-4764-b9e4-e2e7dd358bcb,
abstract = {{At the time of diagnosis, almost 80% of pancreatic cancer patients present with new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic cancer are both associated with low-grade inflammation. Tumour-associated macrophages (TAMs) have a key role in cancer-related inflammation, immune escape, matrix remodelling and metastasis. In this study, the interplay between tumour cells and immune cells under the influence of different glucose levels was investigated. Human peripheral blood mononuclear cells were exposed in vitro to conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour-derived factors stimulated differentiation of macrophages, with a mixed classical (M1-like) and alternatively activated (M2-like) phenotype polarisation (CD11c(+)CD206(+)). High-glucose conditions further enhanced the tumour-driven macrophage enrichment and associated interleukin (IL)-6 and IL-8 cytokine levels. In addition, hyperglycaemia enhanced the responsiveness of tumour-educated macrophages to lipopolysaccharide, with elevated cytokine secretion compared with normal glucose levels. Tumour-educated macrophages were found to promote pancreatic cancer cell invasion in vitro, which was significantly enhanced at high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype polarisation and reduced the tumour cell invasion at normal, but not high, glucose levels. In conclusion, this study demonstrates that pancreatic cancer cells stimulate differentiation of macrophages with pro-tumour properties that are further enhanced by hyperglycaemia. These findings highlight important crosstalk between tumour cells and TAMs in the local tumour microenvironment that may contribute to disease progression in pancreatic cancer patients with hyperglycaemia and T2D.Immunology and Cell Biology advance online publication, 25 March 2014; doi:10.1038/icb.2014.22.}},
author = {{Karnevi, Emelie and Andersson, Roland and Rosendahl, Ann}},
issn = {{1440-1711}},
language = {{eng}},
number = {{6}},
pages = {{543--552}},
publisher = {{Nature Publishing Group}},
series = {{Immunology and Cell Biology}},
title = {{Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion.}},
url = {{https://lup.lub.lu.se/search/files/1490333/4647878.pdf}},
doi = {{10.1038/icb.2014.22}},
volume = {{92}},
year = {{2014}},
}