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

Int J Cancer. 2014 Aug 15;135(4):843-61. doi: 10.1002/ijc.28736. Epub 2014 Feb 5.


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.

Keywords: L1CAM; macrophages; pancreatic cancer; tumor stroma; tumor-associated inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cadherins / metabolism
  • Carcinogenesis
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Cell Shape
  • Cell Transformation, Neoplastic / pathology
  • Coculture Techniques
  • Colonic Neoplasms / metabolism
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Inflammation
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Phenotype
  • Receptors, Cell Surface / metabolism
  • Stromal Cells / cytology
  • Tumor Necrosis Factor-alpha / metabolism


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CDH1 protein, human
  • Cadherins
  • Interleukin-1beta
  • Receptors, Cell Surface
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor