Khabipov Aydar, Miebach Lea, Lenz Maik, Kersting Stephan, Bekeschus Sander
Department of General, Visceral, Thoracic, and Vascular Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany.
ZIK Plasmatis, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany.
Biology (Basel). 2025 Mar 21;14(4):320. doi: 10.3390/biology14040320.
The TME is a critical niche for determining the fate of cancer therapy. Tumor cells often polarize nontumor cells, including immune cells, in the TME to favor cancer growth. In pancreatic cancer, macrophages are associated with poor therapy outcomes and unfavorable survival, especially when rendered into M2 macrophages. The latter show features also found in so-called tumor-associated macrophages (TAM), which are described as protecting and propelling tumor growth. In this context, it has been understudied which pancreatic cancer chemokines contribute to macrophage polarization. To this end, we analyzed murine RAW264.7 macrophages and Panc02 and PDA6606 pancreatic cancer cells in mono- and coculture to identify release patterns of 13 chemokines. Artificial macrophage polarization confirmed prominent changes in surface receptor and chemokine secretion profiles. Strikingly, RAW264.7 cocultures with Panc02 or PDA6606 were congruent in showing elevated levels of CCL2, CCL5, CCL17, CCL20, CCL22, CXCL5, and CXCL10. Further underlining the suitability of our in vitro model, both pancreatic cancer cell lines showed similar modulation of the critical macrophage polarization markers arginase, CD206, and iNOS, as well as chemokine receptors CCR2 and CCR4. Collectively, we demonstrated that our model is suitable for testing the roles and functions of chemokines in macrophage polarization by pancreatic cancer cells.
肿瘤微环境（TME）是决定癌症治疗命运的关键生态位。肿瘤细胞常使TME中的非肿瘤细胞（包括免疫细胞）极化，以促进癌症生长。在胰腺癌中，巨噬细胞与不良的治疗结果和较差的生存率相关，尤其是当它们转变为M2巨噬细胞时。后者还表现出所谓肿瘤相关巨噬细胞（TAM）的特征，TAM被描述为具有保护和推动肿瘤生长的作用。在这种情况下，关于哪些胰腺癌趋化因子促成巨噬细胞极化的研究还很少。为此，我们分析了小鼠RAW264.7巨噬细胞与Panc02和PDA6606胰腺癌细胞在单培养和共培养条件下13种趋化因子的释放模式。人工诱导巨噬细胞极化证实了表面受体和趋化因子分泌谱的显著变化。令人惊讶的是，RAW264.7与Panc02或PDA6606的共培养物中CCL2、CCL5、CCL17、CCL20、CCL22、CXCL5和CXCL10的水平均升高。这两种胰腺癌细胞系对关键的巨噬细胞极化标志物精氨酸酶、CD206和诱导型一氧化氮合酶（iNOS）以及趋化因子受体CCR2和CCR4的调节相似，进一步强调了我们体外模型的适用性。总的来说，我们证明了我们的模型适用于测试趋化因子在胰腺癌细胞诱导巨噬细胞极化中的作用和功能。
