Tumour-educated macrophages display a mixed polarisation and enhance pancreatic cancer cell invasion
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…
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Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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