Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer.
Sci Adv
; 8(41): eabo5224, 2022 10 14.
Article
en En
| MEDLINE
| ID: mdl-36223471
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Megacariocitos
/
Neoplasias
Tipo de estudio:
Qualitative_research
Límite:
Animals
Idioma:
En
Revista:
Sci Adv
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos