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Abstract：
Colorectal cancer, the third most commonly occurring tumor worldwide, poses challenges owing to its high mortality rate and persistent drug resistance in metastatic cases. We investigated the tumor microenvironment, emphasizing the role of cancer-associated fibroblasts in the progression and chemoresistance of colorectal cancer. We used an indirect co-culture system comprising colorectal cancer organoids and cancer-associated fibroblasts to simulate the tumor microenvironment. Immunofluorescence staining validated the characteristics of both organoids and fibroblasts, showing high expression of epithelial cell markers (EPCAM), colon cancer markers (CK20), proliferation markers (KI67), and fibroblast markers (VIM, SMA). Transcriptome profiling was conducted after treatment with anticancer drugs, such as 5-fluorouracil and oxaliplatin, to identify chemoresistance-related genes. Changes in gene expression in the co-cultured colorectal cancer organoids following anticancer drug treatment, compared to monocultured organoids, particularly in pathways related to interferon-alpha/beta signaling and major histocompatibility complex class II protein complex assembly, were identified. These two gene groups potentially mediate drug resistance associated with JAK/STAT signaling. The interaction between colorectal cancer organoids and fibroblasts crucially modulates the expression of genes related to drug resistance. These findings suggest that the interaction between colorectal cancer organoids and fibroblasts significantly influences gene expression related to drug resistance, highlighting potential biomarkers and therapeutic targets for overcoming chemoresistance. Enhanced understanding of the interactions between cancer cells and their microenvironment can lead to advancements in personalized medical research..
摘要：
结直肠癌,全球第三大最常见的肿瘤，由于其在转移性病例中的高死亡率和持续的耐药性，因此提出了挑战。我们调查了肿瘤的微环境,强调癌症相关成纤维细胞在结直肠癌进展和化疗耐药中的作用。我们使用包含结肠直肠癌类器官和癌症相关成纤维细胞的间接共培养系统来模拟肿瘤微环境。免疫荧光染色验证了类器官和成纤维细胞的特征，显示上皮细胞标志物（EPCAM）的高表达，结肠癌标志物（CK20），增殖标志物（KI67），和成纤维细胞标记(VIM，SMA）。转录组分析是在用抗癌药物治疗后进行的，如5-氟尿嘧啶和奥沙利铂，鉴定与化学抗性相关的基因。抗癌药物治疗后共培养的结直肠癌类器官中基因表达的变化，与单一类器官相比，特别是在与干扰素-α/β信号传导和主要组织相容性复合物II类蛋白质复合物组装相关的途径中，已确定。这两个基因群可能介导与JAK/STAT信号相关的药物抗性。结直肠癌类器官和成纤维细胞之间的相互作用至关重要地调节与耐药性相关的基因的表达。这些发现表明结直肠癌类器官和成纤维细胞之间的相互作用显著影响与耐药性相关的基因表达。突出潜在的生物标志物和治疗靶点，以克服化学耐药性。增强对癌细胞与其微环境之间相互作用的理解可以导致个性化医学研究的进步。.
