Metastasized murine oral squamous cell carcinoma cells induce intratumoral polymorphonuclear myeloid derived suppressor cells.
Metastasized murine oral squamous cell carcinoma cells induce intratumoral polymorphonuclear myeloid derived suppressor cells.
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DOI：
10.3892/or.2017.5575
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发表时间：
2017-05
期刊：
影响因子：
4.2
通讯作者：
S. Sumi;Naoki Umemura;E. Takayama;E. Ohkoshi;M. Adachi;M. Mizuno-Kamiya;T. Inagaki;Harumi Kawaki;S. Sumitomo;N. Kondoh
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文献类型：
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作者：
S. Sumi;Naoki Umemura;E. Takayama;E. Ohkoshi;M. Adachi;M. Mizuno-Kamiya;T. Inagaki;Harumi Kawaki;S. Sumitomo;N. Kondoh
髓源性抑制细胞（MDSCs）在炎症或肿瘤组织和肿瘤存在时定位于造血器官和外周血。然而，在原发肿瘤和转移瘤中发现的MDSCs是否存在差异尚不清楚。本研究以Sq-1979小鼠颊黏膜鳞状细胞癌细胞系为基础，建立了转移至淋巴结的肿瘤细胞L5-11细胞系。然后，我们分析了肿瘤的免疫原性，特别是关于MDSCs，以澄清原发肿瘤和转移瘤之间的差异，使用等基因异位肿瘤移植模型。我们的数据显示，21天后，与原代细胞系Sq-1979的同基因移植物相比，淋巴结转移模型中瘤内MDSCs的数量，特别是多形核MDSCs的数量显著增加。此外，我们发现淋巴结转移细胞系增加了促进MDSCs扩张、肿瘤生长和转移的基因表达。因此，这些数据表明肿瘤免疫抑制可以通过激活MDSCs发生。然而，需要进一步的研究来阐明是否需要来自淋巴结转移肿瘤细胞的所有或一部分这些因子来诱导瘤内MDSCs。
Myeloid derived suppressor cells (MDSCs) localize to hematopoietic organs and peripheral blood during inflammation or tumor tissues and lymph nodes in the presence of a tumor. However, whether there are differences in MDSCs found in the primary tumor and metastases is unknown. In the present study, we established a cell line of metastasized tumor cells to a lymph node, L5-11, which were derived from the Sq-1979 mouse buccal mucosa squamous cell carcinoma cell line. We then analyzed tumor immunogenicity, especially with regard to MDSCs, to clarify the differences between the primary tumor and metastases, using an isogenic heterotopic tumor transplantation model. Our data showed that the population of intratumoral MDSCs, especially polymorphonuclear MDSCs in the lymph node metastasis model were significantly increased compared with syngeneic grafts from the primary cell line Sq-1979 after 21 days. Furthermore, we identified that the lymph node metastasis cell line had increased expression of genes that promote the expansion of MDSCs, tumor growth and metastasis. Hence, these data suggest that tumor immunosuppression can occur via activation of MDSCs. However, further examination is required to clarify whether all or a subset of these factors from the lymph node metastasis tumor cells are required to induce intratumoral MDSCs.