结直肠癌（CRC）是全世界最致命的癌症之一。分泌途径的失调是结直肠癌进展的关键驱动因素，因为它调节细胞增殖、血管生成和存活。本研究探讨了 CRC 细胞因子谱的变化，具体取决于培养条件以及成纤维细胞和巨噬细胞作为 2D 和 3D 形成球体中肿瘤微环境的细胞成分的存在。通过对 45 种不同的细胞因子、趋化因子和生长因子进行分析，将 20 个 CRC 细胞系分为高分泌细胞系和低分泌细胞系。在高分泌组中，与血管生成、EMT 和侵袭相关的细胞因子显着上调。 LIF 和 HFG 被认为是两组之间的最佳区分器。与该分组无关，添加正常以及与癌症相关的成纤维细胞通过增加大多数所研究的细胞系中分泌的细胞因子的总量，对细胞因子谱具有类似的影响。相反，正常成纤维细胞与癌症相关成纤维细胞对巨噬细胞的分化和极化的调节不同。总之，我们鉴定了两组细胞因子谱不同的 CRC 细胞系。不仅从肿瘤细胞系而且从体外培养条件详细分析了该谱的依赖性。确定了区分这两组的关键细胞因子，并讨论了它们作为有希望的 CRC 生物标志物候选者的重要性。

Colorectal cancer (CRC) is one of the deadliest cancers worldwide. The dysregulation of secretory pathways is a crucial driver of CRC progression, since it modulates cell proliferation, angiogenesis and survival. This study explores the changes in the CRC cytokine profile depending on the culture conditions and the presence of fibroblasts and macrophages as cellular components of the tumor microenvironment in 2D and in 3D formed spheroids. Upon analysis of 45 different cytokines, chemokines and growth factors, 20 CRC cell lines were categorized into high and low secretors. In the high secretor group cytokines related to angiogenesis, EMT and invasion were significantly upregulated. LIF and HFG were identified as the best discriminator between both groups. Independent of this grouping, the addition of normal as well as cancer-associated fibroblasts had a similar impact on the cytokine profile by increasing the total amount of secreted cytokines in most of the investigated cell lines. In contrast, the differentiation and polarization of macrophages was modulated differently by normal vs. cancer-associated fibroblasts. In summary, we identified two groups of CRC cell lines that differ in their cytokine profile. The dependance of this profile was analyzed in detail-not only from the tumor cell line but as well from the culture condition in vitro. Key cytokines that discriminate the two groups were identified and their importance as promising biomarker candidates for CRC discussed.