Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain.
Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Hospital Universitario Son Espases, Edificio S, 07120 Palma de Mallorca, Spain.
Int J Mol Sci. 2023 Feb 14;24(4):3821. doi: 10.3390/ijms24043821.
Oxaliplatin is successfully used to eradicate micro-metastasis and improve survival, whereas the benefit of adjuvant chemotherapy in the early stages of colorectal cancer remains controversial. Inflammation plays a crucial role in colorectal cancer tumorigenesis. Inflammatory mechanisms are mediated by different immune cells through different cytokines, chemokines, and other proinflammatory molecules that trigger cell progression, an increase of cancer stem cell population, hyperplasia, and metastasis. This study focuses on the analysis of the oxaliplatin effect on tumourspheres formation efficiency, cell viability, cancer stem cells and stemness marker mRNA expression, as well as inflammation-related signature profile expression and its prognosis in primary- and metastatic-derived colorectal tumourspheres derived from colorectal cell lines isolated from the same patient 1 year apart. The results indicate that primary-derived colorectal tumourspheres respond to oxaliplatin, adapting to the adverse conditions through the modulation of CSCs and the stemness properties of tumourspheres. However, metastatic-derived colorectal tumourspheres response led to the release of cytokines and chemokines, promoting an inflammatory process. In addition, the expression of inflammatory markers showing greater difference between primary and metastatic tumours after oxaliplatin treatment correlates with poor prognosis in KM survival studies and is associated with a metastatic phenotype. Our data demonstrated that oxaliplatin triggers an inflammation-related signature profile expression in primary-derived colorectal tumourspheres, related with poor prognosis and a metastatic phenotype, which allow the tumour cells to adapt to the adverse condition. These data highlight the need for of drug testing and personalized medicine in the early stages of colorectal cancer.
奥沙利铂成功用于根除微转移并提高生存率，而辅助化疗在结直肠癌早期的益处仍存在争议。炎症在结直肠癌的肿瘤发生中起着关键作用。炎症机制通过不同的免疫细胞通过不同的细胞因子、趋化因子和其他促炎分子来介导，这些分子触发细胞进展、增加癌症干细胞群体、增生和转移。本研究重点分析奥沙利铂对肿瘤球形成效率、细胞活力、癌症干细胞和干性标志物 mRNA 表达的影响，以及炎症相关特征谱表达及其在原发和转移性结直肠肿瘤球中的预后，这些肿瘤球源自于同一位患者 1 年内分离的结直肠细胞系。结果表明，原发肿瘤球对奥沙利铂有反应，通过调节 CSCs 和肿瘤球的干性特性来适应不利条件。然而，转移性肿瘤球的反应导致细胞因子和趋化因子的释放，从而促进炎症过程。此外，奥沙利铂处理后原发性和转移性肿瘤之间表达的炎症标志物显示出更大的差异，与 KM 生存研究中的不良预后相关，并与转移性表型相关。我们的数据表明，奥沙利铂在原发肿瘤球中触发了与不良预后和转移性表型相关的炎症相关特征谱表达，使肿瘤细胞能够适应不利条件。这些数据强调了在结直肠癌的早期阶段需要进行药物测试和个体化治疗。
