First Author | Roweth HG | Year | 2022 |
Journal | Sci Adv | Volume | 8 |
Issue | 41 | Pages | eabo5224 |
PubMed ID | 36223471 | Mgi Jnum | J:330589 |
Mgi Id | MGI:7379719 | Doi | 10.1126/sciadv.abo5224 |
Citation | Roweth HG, et al. (2022) Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer. Sci Adv 8(41):eabo5224 |
abstractText | 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. |