Fernández-Domínguez Ileana J, Pérez-Cárdenas Enrique, Taja-Chayeb Lucia, Wegman-Ostrosky Talia, Caro-Sánchez Claudia H S, Zentella-Dehesa Alejandro, Dueñas-González Alfonso, López-Basabe Horacio, Morales-Bárcenas Rocío, Trejo-Becerril Catalina
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, México City, Mexico.
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México. Edificio D, 1° Piso, Circuito de Posgrados, Ciudad Universitaria, México City, Mexico.
Front Cell Dev Biol. 2025 Mar 28;13:1499936. doi: 10.3389/fcell.2025.1499936. eCollection 2025.
The study and characterization of cell-free DNA (cfDNA) has gained significant importance due to its clinical applications as a diagnostic and prognostic marker. However, it remains unclear whether all cell populations within a tumor or culture contribute equally to its release. This pioneering research analyzes the contribution of cancer stem cells (CSCs) in colon cancer cell lines to the amount of cfDNA released and its role in cellular transformation.
The CSC population derived from the SW480 colon cancer cell line was enriched using a non-adhesive culture system to assess the quantity and electrophoretic profile of the released cfDNA. Subsequently, transformation assays were conducted to compare the transforming capacity of the cfDNA obtained from enriched cultures with that from non-enriched cultures. Group differences were analyzed using analysis of variance (ANOVA), followed by interpretation with Tukey's test.
Our study revealed that cultures with CSCs released greater amounts of cfDNA, displaying a distinct fragment profile. Additionally, cfDNA from different cellular origins influenced the transformation characteristics of NIH3T3 cells. This is the first demonstration of a link between CSC proportions and cfDNA release, suggesting that CSCs and microenvironmental conditions can affect cfDNA quantity and its potential to induce transformation.
These findings highlight the importance of cfDNA in carcinogenesis and its potential as a biomarker and therapeutic target, especially given the role of CSCs in drug resistance and tumor aggressiveness.
由于游离DNA(cfDNA)作为诊断和预后标志物的临床应用,对其研究和表征已变得极为重要。然而,肿瘤或培养物中的所有细胞群体对其释放的贡献是否相同仍不清楚。这项开创性研究分析了结肠癌干细胞(CSC)对释放的cfDNA量的贡献及其在细胞转化中的作用。
使用非贴壁培养系统富集源自SW480结肠癌细胞系的CSC群体,以评估释放的cfDNA的数量和电泳图谱。随后,进行转化试验,比较从富集培养物中获得的cfDNA与未富集培养物中获得的cfDNA的转化能力。使用方差分析(ANOVA)分析组间差异,随后用Tukey检验进行解释。
我们的研究表明,含有CSC的培养物释放出更多的cfDNA,呈现出独特的片段图谱。此外,来自不同细胞来源的cfDNA影响了NIH3T3细胞的转化特性。这是首次证明CSC比例与cfDNA释放之间存在联系,表明CSC和微环境条件可影响cfDNA的数量及其诱导转化的潜力。
这些发现突出了cfDNA在致癌作用中的重要性及其作为生物标志物和治疗靶点的潜力,特别是考虑到CSC在耐药性和肿瘤侵袭性中的作用。