Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer.
Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer.
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DOI：
10.1126/sciadv.abo5224
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发表时间：
2022-10-14
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
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尽管大量研究表明，血小板可以促进肿瘤细胞的转移，但原发肿瘤是否会影响产生血小板的巨核细胞仍未得到充分的研究。在这项研究中，我们使用了一种自发的乳腺癌小鼠模型，以表明肿瘤负荷减少了巨核细胞的数量和大小，并破坏了多倍化。单细胞RNA测序表明，荷瘤小鼠的巨核细胞表现出促炎表型，表现为Ctsg、Lcn2、S100A8和S100A9转录增加。血小板中S100A8/A9蛋白和Lipocalin-2水平也增加，提示肿瘤引起的巨核细胞的变化传递给其后代，这在更大程度上促进了肿瘤细胞的体外侵袭和肿瘤细胞的肺定植。我们的研究首次证明了乳腺癌引起的巨核细胞的改变，导致了血小板含量的质变，这可能会反馈促进肿瘤转移。乳腺癌会产生促炎症的巨核细胞，产生“超级充电”的血小板，从而加剧肿瘤细胞的转移。
Despite abundant research demonstrating that platelets can promote tumor cell metastasis, whether primary tumors affect platelet-producing megakaryocytes remains understudied. In this study, we used a spontaneous murine model of breast cancer to show that tumor burden reduced megakaryocyte number and size and disrupted polyploidization. Single-cell RNA sequencing demonstrated that megakaryocytes from tumor-bearing mice exhibit a pro-inflammatory phenotype, epitomized by increased Ctsg, Lcn2, S100a8, and S100a9 transcripts. Protein S100A8/A9 and lipocalin-2 levels were also increased in platelets, suggesting that tumor-induced alterations to megakaryocytes are passed on to their platelet progeny, which promoted in vitro tumor cell invasion and tumor cell lung colonization to a greater extent than platelets from wild-type animals. Our study is the first to demonstrate breast cancer–induced alterations in megakaryocytes, leading to qualitative changes in platelet content that may feedback to promote tumor metastasis. Breast cancer creates pro-inflammatory megakaryocytes, producing “super-charged” platelets that exacerbate tumor cell metastasis.
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影响因子：
4.7
作者：
Braun A;Anders HJ;Gudermann T;Mammadova-Bach E
通讯作者：
Mammadova-Bach E
DOI：
10.1111/jth.13302
发表时间：
2016-05
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Bye AP;Unsworth AJ;Gibbins JM
通讯作者：
Gibbins JM
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
13.6
作者：
Barrett TJ;Cornwell M;Myndzar K;Rolling CC;Xia Y;Drenkova K;Biebuyck A;Fields AT;Tawil M;Luttrell-Williams E;Yuriditsky E;Smith G;Cotzia P;Neal MD;Kornblith LZ;Pittaluga S;Rapkiewicz AV;Burgess HM;Mohr I;Stapleford KA;Voora D;Ruggles K;Hochman J;Berger JS
通讯作者：
Berger JS
影响因子：
3.7
作者：
Chen B;Miller AL;Rebelatto M;Brewah Y;Rowe DC;Clarke L;Czapiga M;Rosenthal K;Imamichi T;Chen Y;Chang CS;Chowdhury PS;Naiman B;Wang Y;Yang D;Humbles AA;Herbst R;Sims GP
通讯作者：
Sims GP