SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II

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dc.citation.firstpageE219
dc.citation.issueNumber5
dc.citation.journalTitleInternational Journal of Cancer
dc.citation.lastpageE229
dc.citation.volumeNumber136
dc.contributor.authorChoi, Dong Soon
dc.contributor.authorStark, Daniel J.
dc.contributor.authorRaphael, Robert M.
dc.contributor.authorWen, Jianguo
dc.contributor.authorSu, Jing
dc.contributor.authorZhou, Xiaobo
dc.contributor.authorChang, Chung-Che
dc.contributor.authorZu, Youli
dc.date.accessioned2017-05-30T17:03:41Z
dc.date.available2017-05-30T17:03:41Z
dc.date.issued2015
dc.description.abstractMultiple myeloma (MM) is a B lymphocyte malignancy that remains incurable despite extensive research efforts. This is due, in part, to frequent disease recurrences associated with the persistence of myeloma cancer stem cells (mCSCs). Bone marrow mesenchymal stromal cells (BMSCs) play critical roles in supporting mCSCs through genetic or biochemical alterations. Previously, we identified mechanical distinctions between BMSCs isolated from MM patients (mBMSCs) and those present in the BM of healthy individuals (nBMSCs). These properties of mBMSC contributed to their ability to preferentially support mCSCs. To further illustrate mechanisms underlying the differences between mBMSCs and nBMSCs, here we report that (i) mBMSCs express an abnormal, constitutively high level of phosphorylated Myosin II, which leads to stiffer membrane mechanics, (ii) mBMSCs are more sensitive to SDF-1α-induced activation of MYL2 through the G(i./o)-PI3K-RhoA-ROCK-Myosin II signaling pathway, affecting Young's modulus in BMSCs and (iii) activated Myosin II confers increased cell contractile potential, leading to enhanced collagen matrix remodeling and promoting the cell–cell interaction between mCSCs and mBMSCs. Together, our findings suggest that interfering with SDF-1α signaling may serve as a new therapeutic approach for eliminating mCSCs by disrupting their interaction with mBMSCs.
dc.identifier.citationChoi, Dong Soon, Stark, Daniel J., Raphael, Robert M., et al.. "SDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II." <i>International Journal of Cancer,</i> 136, no. 5 (2015) Wiley: E219-E229. http://dx.doi.org/10.1002/ijc.29145.
dc.identifier.doihttp://dx.doi.org/10.1002/ijc.29145
dc.identifier.urihttps://hdl.handle.net/1911/94739
dc.language.isoeng
dc.publisherWiley
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Wiley.
dc.subject.keywordRhoA-ROCK-Myosin II
dc.subject.keywordSDF-1α
dc.subject.keywordmesenchymal stromal cells
dc.subject.keywordmultiple myeloma
dc.titleSDF-1α stiffens myeloma bone marrow mesenchymal stromal cells through the activation of RhoA-ROCK-Myosin II
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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