Regulatory role of echinochrome A in cancer-associated fibroblast-mediated lung cancer cell migration. Regulatory role of echinochrome A in cancer-associated fibroblast-mediated lung cancer cell migration

Echinochrome A (Ech A), a marine biosubstance isolated from sea urchins, is a strong antioxidant, and its clinical form, histochrome, is being used to treat several diseases, such as ophthalmic, cardiovascular, and metabolic diseases. Cancer-associated fibroblasts (CAFs) are a component of the tumor stroma and induce phenotypes related to tumor malignancy, including epithelial–mesenchymal transition (EMT) and cancer stemness, through reciprocal interactions with cancer cells. Here, we investigated whether Ech A modulates the properties of CAFs and alleviates CAF-induced lung cancer cell migration. Interestingly, the secretion of several cytokines and chemokines stimulating cancer cell metastasis was reduced in CAF-like MRC5 cells treated with Ech A compared to untreated MRC5 cells. Moreover, while conditioned medium from MRC5 cells enhanced the migration of non-small cell lung cancer cells, conditioned medium from MRC5 cells treated with Ech A suppressed cancer cell migration. In conclusion, we suggest that Ech A might be a potent adjuvant that increases the efficacy of cancer treatments to mitigate lung cancer progression. Overall design: To characterize the regulatory effect of Ech A on gene expression, we performed mRNA transcriptome analysis in MRC5 cells treated with or without Ech A. Samples were collected at both the 24 h and 72 h time points under each experimental condition, and differences in gene expression were analyzed by comparing the values at 72 h with those at 24 h.

Echinochrome A (Ech A)是一种从海胆中分离得到的海洋生物活性物质，属于强效抗氧化剂；其临床制剂histochrome已被用于治疗多种疾病，涵盖眼科疾病、心血管疾病及代谢性疾病。癌症相关成纤维细胞（Cancer-associated fibroblasts, CAFs）是肿瘤间质的组成成分，可通过与癌细胞的双向相互作用，诱导与肿瘤恶性表型相关的多种生物学过程，包括上皮间质转化（epithelial–mesenchymal transition, EMT）及肿瘤干细胞干性。本研究旨在探讨Ech A是否可调控CAFs的生物学特性，并缓解CAFs诱导的肺癌细胞迁移能力。值得注意的是，与未处理的MRC5细胞相比，经Ech A处理的类CAFs MRC5细胞中，多种可促进癌细胞转移的细胞因子及趋化因子的分泌水平显著降低。此外，未经处理的MRC5细胞条件培养基可增强非小细胞肺癌细胞的迁移能力，而经Ech A处理的MRC5细胞条件培养基则可抑制癌细胞迁移。综上，本研究提示Ech A或可作为一种强效辅助治疗剂，提升癌症治疗疗效，以延缓肺癌进展。总体实验设计：为表征Ech A对基因表达的调控作用，我们对经或未经Ech A处理的MRC5细胞开展了mRNA转录组分析。在每种实验条件下，分别于24 h及72 h两个时间点收集样本，并通过比较72 h与24 h的基因表达量差异，分析基因表达变化情况。