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血小板通过上调 IL-1β 促进多发性骨髓瘤进展。

Platelets Enhance Multiple Myeloma Progression via IL-1β Upregulation.

机构信息

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

出版信息

Clin Cancer Res. 2018 May 15;24(10):2430-2439. doi: 10.1158/1078-0432.CCR-17-2003. Epub 2018 Feb 9.

Abstract

Tumor cell-platelet interactions contribute to tumor progression and metastasis in solid tumors. However, the role of platelets in hematological malignancies is not clear. We investigated the association of platelet activation status with clinical stages in multiple myeloma (MM) patients and explored the role of platelets in MM progression. Platelets were obtained from healthy donors and MM patients. We examined platelet activation status in MM patients by flow cytometry and transmission electron microscopy. We also observed the enriched pathways that are involved with platelet activation in RNA sequencing of platelets. MM cell lines were used to assess the effect of platelets on MM cell proliferation and their engraftment RNA sequencing of MM cell lines was performed to explore molecular mechanisms underlying MM cell-platelet interaction and a CRISPR/Cas9 knockout approach was used for validation. Platelets from MM patients were highly activated with disease progression. RNA sequencing of platelets revealed that genes involved in platelets were enriched in patients with smoldering MM (SMM) or MM. Platelets promoted MM cell proliferation and contributed to tumor engraftment in bone marrow RNA sequencing revealed that was upregulated in MM cell lines co-cultured with platelets, whereas knockout in MM cell lines abrogated the effects of platelets on MM cell proliferation and engraftment Platelets from MM patients were highly activated with disease progression. IL-1β is critical to platelet-mediated MM progression and might be a potential target for MM treatment. .

摘要

肿瘤细胞-血小板相互作用促进实体瘤的肿瘤进展和转移。然而,血小板在血液恶性肿瘤中的作用尚不清楚。我们研究了血小板激活状态与多发性骨髓瘤(MM)患者临床分期的相关性,并探讨了血小板在 MM 进展中的作用。从健康供体和 MM 患者中获得血小板。我们通过流式细胞术和透射电子显微镜检查 MM 患者的血小板激活状态。我们还观察了富含血小板激活途径的 RNA 测序中的血小板。使用 MM 细胞系评估血小板对 MM 细胞增殖及其在骨髓中的植入的影响。对 MM 细胞系进行 RNA 测序以探讨 MM 细胞-血小板相互作用的分子机制,并使用 CRISPR/Cas9 敲除方法进行验证。随着疾病的进展,MM 患者的血小板高度激活。血小板的 RNA 测序显示,与冒烟型 MM(SMM)或 MM 患者中涉及血小板的基因富集。血小板促进 MM 细胞增殖,并有助于骨髓中的肿瘤植入。RNA 测序显示,与血小板共培养的 MM 细胞系中上调,而 MM 细胞系中敲除则消除了血小板对 MM 细胞增殖和植入的影响。随着疾病的进展,MM 患者的血小板高度激活。IL-1β 对血小板介导的 MM 进展至关重要,可能是 MM 治疗的潜在靶点。

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