Interaction Between Pancreatic Cancer Cells and Tumor-Associated Macrophages Promotes the Invasion of Pancreatic Cancer Cells and the Differentiation and Migration of Macrophages

In this study, the impact of pancreatic cancer cell interaction with macrophages on the differentiation and function of macrophages and the behaviors of pancreatic cancer cells in vitro is evaluated. The expression of immunocompetent cell-associated markers in 22 pancreatic cancer specimens was characterized by immunohistochemistry. The impact of pancreatic cancer cells (PANC-1 and BxPC-3) on the differentiation and migration of human U937 monocytes and the effect of U937-derived macrophages on the proliferation and invasion of PANC-1 and BxPC-3 were determined by transwell assays. The potential effect on U937-derived macrophages or on the behaviors of pancreatic cancer cells following coculture in a transwell system was analyzed by quantitative real-time polymerase chain reaction. The high levels of macrophage-related CD68 and CD163 expression were detected in the pancreatic cancer specimens. Pancreatic cancer cells promoted the differentiation of U937 cells and migration of U937-derived macrophages, but decreased the mRNA transcripts of macrophage polarization-related genes of interleukin (IL)-10, IL-12p40, inducible nitric oxide synthase (iNOS), and CD163, particularly for iNOS. Furthermore, U937-derived M2 macrophages inhibited the proliferation of pancreatic cancer cells, but promoted their invasion. Coculture of pancreatic cancer cells with U937-derived macrophages upregulated the mRNA expression of genes associated with the epithelial-mesenchymal transition process, angiogenesis, and stemness of pancreatic cancer, but downregulated the expression of E-cadherin in pancreatic cancer cells. The interaction between pancreatic cancer cells and tumor-associated macrophages may play a pivotal role in the progression of pancreatic cancer. (c) 2014 IUBMB Life, 66(12):835-846, 2014