CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity

International Journal of Molecular Sciences

Péter Lőrincz¹  Idan Carmi²  Edit I. Buzás²  Zoltán Wiener²  Iván Seress²  Andrea Kelemen²  Tamás Tölgyes³  Attila Bursics³  Kristóf Dede³ 

[1] Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University of Sciences, H-1117 Budapest, Hungary;Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089 Budapest, Hungary;Uzsoki Hospital, H-1145 Budapest, Hungary;

关键词: exosome;    cancer stem cell;    organoid;    cancer-associated fibroblast;    CD44;    CD133;   

DOI  :  10.3390/ijms23042180

来源: DOAJ

【 摘 要 】

Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44^high cells produce more organoids with a higher proliferation intensity, as compared to CD44^low cells. Interestingly, we detected an increased EV release by CD44^high CRC cells. In addition, we found that the miRNA cargos of CD44^high and CD44^low cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44^high cells induced the proliferation and activation of colon fibroblasts more strongly than CD44^low cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation.

【 授权许可】

Unknown