Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer

Roweth, H. G. ORCID: https://orcid.org/0000-0002-1100-8409, Malloy, M. W., Goreczny, G. J., Becker, I. C., Guo, Q., Mittendorf, E. A., Italiano Jr., J. E., McAllister, S. S. and Battinelli, E. M. (2022) Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer. Science Advances, 8 (41). ISSN 2375-2548 doi: 10.1126/sciadv.abo5224

Abstract/Summary

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.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/127724
Identification Number/DOI	10.1126/sciadv.abo5224
Refereed	Yes
Divisions	No Reading authors. Back catalogue items Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	American Association for the Advancement of Science
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