Sabanovic Berina, Giulietti Matteo, Cecati Monia, Spolverato Gaya, Benna Clara, Pucciarelli Salvatore, Piva Francesco
Department of Specialistic Clinical and Odontostomatological Sciences, Polytechnic University of Marche, 60131 Ancona, Italy.
Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35122 Padua, Italy.
Biomedicines. 2022 Oct 15;10(10):2588. doi: 10.3390/biomedicines10102588.
Pancreatic ductal adenocarcinoma (PDAC) has high metastatic potential. The "genometastasis" theory proposes that the blood of some cancer patients contains elements able to transform healthy cells by transferring oncogenes. Since findings on genometastasis in PDAC are still scarce, we sought supporting evidence by treating non-tumour HEK293T and hTERT-HPNE human cell lines with sera of PDAC patients. Here, we showed that HEK293T cells have undergone malignant transformation, increased the migration and invasion abilities, and acquired a partial chemoresistance, whereas hTERT-HPNE cells were almost refractory to transformation by patients' sera. Next-generation sequencing showed that transformed HEK293T cells gained and lost several genomic regions, harbouring genes involved in many cancer-associated processes. Our results support the genometastasis theory, but further studies are needed for the identification of the circulating transforming elements. Such elements could also be useful biomarkers in liquid biopsy assays.
胰腺导管腺癌(PDAC)具有很高的转移潜能。“基因组转移”理论提出,一些癌症患者的血液中含有能够通过转移致癌基因来转化健康细胞的成分。由于关于PDAC中基因组转移的研究结果仍然很少,我们通过用PDAC患者的血清处理非肿瘤性HEK293T和hTERT - HPNE人细胞系来寻找支持证据。在此,我们表明HEK293T细胞发生了恶性转化,迁移和侵袭能力增强,并获得了部分化疗耐药性,而hTERT - HPNE细胞对患者血清的转化几乎具有抗性。二代测序显示,转化后的HEK293T细胞获得和丢失了几个基因组区域,其中包含参与许多癌症相关过程的基因。我们的结果支持基因组转移理论,但需要进一步研究来鉴定循环中的转化成分。这些成分也可能成为液体活检检测中的有用生物标志物。