Osterix-Cre marks distinct subsets of CD45- and CD45+ stromal populations in extra-skeletal tumors with pro-tumorigenic characteristics

eLife

Roberto Civitelli¹  Jad I Belle²  Hamza Celik²  Francesca Fontana²  Biancamaria Ricci³  Roberta Faccio³  Eric Tycksen⁴ 

[1] Department of Medicine, Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, United States;Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, United States;Department of Orthopedics, Washington University School of Medicine, St. Louis, United States;Genome Technology Access Center, Department of Genetics, Washington University School of Medicine, St. Louis, United States;

关键词: osterix;    cancer;    TME;    CAF;    bone;    HSC;   

DOI  :  10.7554/eLife.54659

来源: DOAJ

【 摘 要 】

Cancer-associated fibroblasts (CAFs) are a heterogeneous population of mesenchymal cells supporting tumor progression, whose origin remains to be fully elucidated. Osterix (Osx) is a marker of osteogenic differentiation, expressed in skeletal progenitor stem cells and bone-forming osteoblasts. We report Osx expression in CAFs and by using Osx-cre;TdTomato reporter mice we confirm the presence and pro-tumorigenic function of TdTOSX+ cells in extra-skeletal tumors. Surprisingly, only a minority of TdTOSX+ cells expresses fibroblast and osteogenic markers. The majority of TdTOSX+ cells express the hematopoietic marker CD45, have a genetic and phenotypic profile resembling that of tumor infiltrating myeloid and lymphoid populations, but with higher expression of lymphocytic immune suppressive genes. We find Osx transcript and Osx protein expression early during hematopoiesis, in subsets of hematopoietic stem cells and multipotent progenitor populations. Our results indicate that Osx marks distinct tumor promoting CD45- and CD45+ populations and challenge the dogma that Osx is expressed exclusively in cells of mesenchymal origin.

【 授权许可】

Unknown