TGFβ携带的质体外囊泡在血浆中:成为头颈鳞状细胞癌患者癌症进展潜在生物标志物。
TGFβ carrying exosomes in plasma: potential biomarkers of cancer progression in patients with head and neck squamous cell carcinoma.
发表日期:2023 Feb 21
作者:
Nils Ludwig, Saigopalakrishna S Yerneni, Malgorzata Harasymczuk, Mirosław J Szczepański, Alicja Głuszko, Wojciech Kukwa, Theresa Jordan, Gerrit Spanier, Juergen Taxis, Steffen Spoerl, Johannes K Meier, Cynthia S Hinck, Phil G Campbell, Torsten E Reichert, Andrew P Hinck, Theresa L Whiteside
来源:
BRITISH JOURNAL OF CANCER
摘要:
TGFβ对癌症进展的贡献得到了广泛的文献报道。然而,血浆中TGFβ水平通常不与临床病理数据相关。我们研究了从小鼠和人血浆中分离出的外泌体携带的TGFβ在头颈鳞癌(HNSCC)疾病进展中的作用。使用4-硝基喹啉-1-氧化物(4-NQO)小鼠模型研究口腔癌发生过程中TGFβ表达水平的变化。在人HNSCC中,确定了TGFβ和Smad3蛋白表达水平和TGFB1基因表达。使用ELISA和TGFβ生物活性检测评估可溶性TGFβ水平。使用大小排除色谱法从血浆中分离出外泌体,并使用生物活性检测和生物印迹微阵列定量TGFβ含量。4-NQO致癌过程中,随着肿瘤进展,肿瘤组织和血清中的TGFβ水平增加。循环外泌体中的TGFβ含量也增加。在HNSCC患者中,肿瘤组织中TGFβ、Smad3和TGFB1过度表达,并与可溶性TGFβ水平增加相关。肿瘤中的TGFβ表达和可溶性TGFβ水平都与临床病理数据或生存率无关。只有与外泌体相关的TGFβ反映了肿瘤进展并与肿瘤大小相关。在HNSCC患者血浆中的循环TGFβ+外泌体显示出潜在的无创生物标志物作用。©2023。作者(们)独家授权Springer Nature Limited。
Contributions of TGFβ to cancer progression are well documented. However, plasma TGFβ levels often do not correlate with clinicopathological data. We examine the role of TGFβ carried in exosomes isolated from murine and human plasma as a contributor to disease progression in head and neck squamous cell carcinoma (HNSCC).The 4-nitroquinoline-1-oxide (4-NQO) mouse model was used to study changes in TGFβ expression levels during oral carcinogenesis. In human HNSCC, TGFβ and Smad3 protein expression levels and TGFB1 gene expression were determined. Soluble TGFβ levels were evaluated by ELISA and TGFβ bioassays. Exosomes were isolated from plasma using size exclusion chromatography, and TGFβ content was quantified using bioassays and bioprinted microarrays.During 4-NQO carcinogenesis, TGFβ levels in tumour tissues and in serum increased as the tumour progressed. The TGFβ content of circulating exosomes also increased. In HNSCC patients, TGFβ, Smad3 and TGFB1 were overexpressed in tumour tissues and correlated with increased soluble TGFβ levels. Neither TGFβ expression in tumours nor levels of soluble TGFβ correlated with clinicopathological data or survival. Only exosome-associated TGFβ reflected tumour progression and correlated with tumour size.Circulating TGFβ+ exosomes in the plasma of patients with HNSCC emerge as potential non-invasive biomarkers of disease progression in HNSCC.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.