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

Menée in vitro et à l'aide de modèles murins de cancer mammaire, cette étude met en évidence un phénotype pro-inflammatoire au niveau des mégacaryocytes et démontre que les plaquettes sanguines issues de la fragmentation de ces cellules favorisent le développement de métastases

Résumé en anglais

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.