Platelets enhance multiple myeloma progression via il-1b upregulation

Satoshi Takagi, Shokichi Tsukamoto, Jihye Park, Kelly E. Johnson, Yawara Kawano, Michele Moschetta, Chia Jen Liu, Yuji Mishima, Katsutoshi Kokubun, Salomon Manier, Karma Z. Salem, Daisy Huynh, Antonio Sacco, Jodi Forward, Aldo M. Roccaro, Elisabeth M. Battinelli, Irene M. Ghobrial*

*此作品的通信作者

研究成果: Article同行評審

46 引文 斯高帕斯(Scopus)

摘要

Purpose: 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. Experimental Design: 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 in vitro and their engraftment in vivo. 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. Results: 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 in vitro and contributed to tumor engraftment in bone marrow in vivo. RNA sequencing revealed that IL-1b was upregulated in MM cell lines co-cultured with platelets, whereas IL-1b knockout in MM cell lines abrogated the effects of platelets on MM cell proliferation and engraftment in vivo. Conclusions: Platelets from MM patients were highly activated with disease progression. IL-1b is critical to platelet-mediated MM progression and might be a potential target for MM treatment.

原文English
頁(從 - 到)2430-2439
頁數10
期刊Clinical Cancer Research
24
發行號10
DOIs
出版狀態Published - 15 5月 2018

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