Multiple myeloma dell-derived microvesicles are enriched in CD147 expression and enhance tumor cell proliferation.
Multiple myeloma dell-derived microvesicles are enriched in CD147 expression and enhance tumor cell proliferation.
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DOI：
10.18632/oncotarget.2159
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发表时间：
2014-07-30
期刊：
影响因子：
--
通讯作者：
Jelinek DF
中科院分区：
文献类型：
--
作者：
Arendt BK;Walters DK;Wu X;Tschumper RC;Jelinek DF
多发性骨髓瘤(MM)的特征是恶性浆细胞在骨髓中克隆性扩张。越来越多的文献表明，肿瘤细胞释放具有生物活性的微囊泡(MVS)，改变局部和远处的微环境。在这项研究中，我们的目标是确定MM细胞是否释放MVS，如果是的话，开始表征它们的生物学活性。在这里，我们提出了明确的证据，不仅患者MM细胞和人类MM细胞系(HMCL)都能释放MVS，而且这些MVS能刺激MM细胞的生长。有趣的是，MM来源的MVS富含生物活性形式的CD147，这是一种我们先前证明对MM细胞增殖至关重要的跨膜分子。利用从稳定转染CD147-GFP融合构建体(CD147-GFP)的HMCL中分离出的MVS，我们观察到MV来源的CD147与HMCL的结合和内化。CD147GFP内化程度较高的细胞增殖速度高于CD147GFP关联度较低的细胞。最后，从CD147下调的HMCL获得的MVS刺激HMCL增殖的能力减弱。综上所述，本研究证实了MV脱落和MV介导的细胞间通讯在恶性浆细胞增殖中的意义，并确定了MV丰富的CD147在这一过程中的作用。
Multiple myeloma (MM) is characterized by the clonal expansion of malignant plasma cells within the bone marrow. There is a growing literature that tumor cells release biologically active microvesicles (MVs) that modify both local and distant microenvironments. In this study, our goals were to determine if MM cells release MVs, and if so, begin to characterize their biologic activity. Herein we present clear evidence that not only do both patient MM cells and human MM cell lines (HMCLs) release MVs, but that these MVs stimulate MM cell growth. Of interest, MM-derived MVs were enriched with the biologically active form of CD147, a transmembrane molecule previously shown by us to be crucial for MM cell proliferation. Using MVs isolated from HMCLs stably transfected with a CD147-GFP fusion construct (CD147GFP), we observed binding and internalization of MV-derived CD147 with HMCLs. Cells with greater CD147GFP internalization proliferated at a higher rate than did cells with less CD147GFP association. Lastly, MVs obtained from CD147 downregulated HMCLs were attenuated in their ability to stimulate HMCL proliferation. In summary, this study demonstrates the significance of MV shedding and MV-mediated intercellular communication on malignant plasma cell proliferation, and identifies the role of MV-enriched CD147 in this process.
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
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作者：
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作者：
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影响因子：
8.2
作者：
Liu, Yan;Zhu, Xiao-jian;Li, Qiu-bai
通讯作者：
Li, Qiu-bai
DOI：
10.1073/pnas.0804543106
发表时间：
2009-03-10
影响因子：
11.1
作者：
Al-Nedawi, Khalid;Meehan, Brian;Rak, Janusz
通讯作者：
Rak, Janusz