Extracellular Ubiquitin is the Causal Link between Stored Blood Transfusion Therapy and Tumor Progression in a Melanoma Mouse Model
Extracellular Ubiquitin is the Causal Link between Stored Blood Transfusion Therapy and Tumor Progression in a Melanoma Mouse Model
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细胞外泛素是黑色素瘤小鼠模型中储存的输血疗法与肿瘤进展之间的因果关系
DOI：
10.7150/jca.31360
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Xia, Rong
中科院分区：
文献类型：
--
作者：
Zhang, Jingjun;Chen, Shuying;Xia, Rong
背景资料：已储存一段时间的血液的输血被发现与癌症患者的输血相关免疫调节（TRIM）反应相关，这可能导致不良的临床结果，例如肿瘤复发、转移和存活率降低。鉴于本研究的研究者先前观察到全血中的泛素含量与储存时间之间的正相关性，假设这可能是储存血液的输血与癌症预后不良之间的因果关系。研究方法：在本研究中，使用黑色素瘤小鼠模型，通过多种细胞生物学方法，如流式细胞术和免疫组织化学，研究储存血液中存在的泛素对癌症预后的潜在临床影响。结果如下：细胞外泛素和输注由泛素组成的储存小鼠血液都降低了黑色素瘤细胞的凋亡率，促进了肺肿瘤转移和肿瘤进展，并降低了黑色素瘤小鼠的长期生存率。此外，在存在泛素的情况下观察到肿瘤标志物和致瘤性TH2细胞因子产生的上调以及免疫细胞数量的减少。结论：目前的研究结果提供了新的见解泛素在免疫调节中的作用，在黑色素瘤小鼠模型，并建议泛素之间的因果关系异体输血治疗和癌症预后不良。
Background: The transfusion of blood that has been stored for some time was found to be associated with transfusion-related immune modulation (TRIM) responses in cancer patients, which could result in poor clinical outcomes, such as tumor recurrence, metastasis and reduced survival rate. Given the prior observation of the positive correlation between ubiquitin content in whole blood and storage duration by the investigators of the present study, it was hypothesized that this could be the causal link behind the association between the transfusion of stored blood and poor cancer prognosis. Methods: In the present study, a melanoma mouse model was used to study the potential clinical impact of ubiquitin present in stored blood on cancer prognosis through a variety of cell biology methods, such as flow cytometry and immunohistochemistry. Results: Both extracellular ubiquitin and the infusion of stored mice blood that comprised of ubiquitin reduced the apoptotic rate of melanoma cells, promoted lung tumor metastasis and tumor progression, and reduced the long-term survival rate of melanoma mice. In addition, the upregulation of tumor markers and tumorigenic TH2 cytokine generation, as well as reduced immune cell numbers, were observed in the presence of ubiquitin. Conclusions: The present findings provide novel insights into the role of ubiquitin in immune regulation in a melanoma mouse model, and suggest ubiquitin as the causal link between allogeneic blood transfusion therapy and poor cancer prognosis.