Tumor‐associated macrophages exhibit pro‐ and anti‐inflammatory properties by which they impact on pancreatic tumorigenesis

Pancreatic ductal adenocarcinoma (PDAC) still ranking 4th in the order of fatal tumor diseases is characterized by a profound tumor stroma with high numbers of tumor‐associated macrophages (TAMs). Driven by environmental factors, monocytes differentiate into M1‐ or M2‐macrophages, the latter commonly regarded as being protumorigenic. Because a detailed analysis of TAMs in human PDAC development is still lacking, freshly isolated PDAC‐derived TAMs were analyzed for their phenotype and impact on epithelial‐mesenchymal‐transition (EMT) of benign (H6c7) and malignant (Colo357) pancreatic ductal epithelial cells. TAMs exhibited characteristics of M1‐macrophages (expression of HLA‐DR, IL‐1β, or TNF‐α) and M2‐macrophages (expression of CD163 and IL‐10). In the presence of TAMs, H6c7, and Colo357 cells showed an elongated cell shape along with an increased expression of mesenchymal markers such as vimentin and reduced expression of epithelial E‐cadherin. Similar to TAMs, in vitro generated M1‐ and M2‐macrophages both mediated EMT in H6c7 and Colo357 cells. M1‐macrophages acquired M2‐characteristics during coculture that could be prevented by GM‐CSF treatment. However, M1‐macrophages still potently induced EMT in H6c7 and Colo357 cells although lacking M2‐characteristics. Overall, these data demonstrate that TAMs exhibit anti‐ as well as proinflammatory properties that equally contribute to EMT induction in PDAC initiation and development.