| Literature DB >> 34911937 |
Ved P Sharma1,2, Binwu Tang3, Yarong Wang1,2,4, Camille L Duran1, George S Karagiannis1,4, Emily A Xue1, David Entenberg1,2,4, Lucia Borriello1, Anouchka Coste1,5, Robert J Eddy1, Gina Kim1, Xianjun Ye1, Joan G Jones1,4,6,7, Eli Grunblatt8, Nathan Agi8, Sweta Roy8, Gargi Bandyopadhyaya8, Esther Adler9, Chinmay R Surve1,4, Dominic Esposito10, Sumanta Goswami1,8, Jeffrey E Segall1,2, Wenjun Guo11,12, John S Condeelis13,14,15,16, Lalage M Wakefield17, Maja H Oktay18,19,20,21.
Abstract
Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. Here, we employ high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is the hallmark of disseminating tumor cells. CSCs are enriched near macrophages, particularly near macrophage-containing intravasation sites called Tumor Microenvironment of Metastasis (TMEM) doorways. Substantial enrichment of CSCs occurs on association with TMEM doorways, contributing to the finding that CSCs represent >60% of circulating tumor cells. Mechanistically, stemness is induced in non-stem cancer cells upon their direct contact with macrophages via Notch-Jagged signaling. In breast cancers from patients, the density of TMEM doorways correlates with the proportion of cancer cells expressing stem cell markers, indicating that in human breast cancer TMEM doorways are not only cancer cell intravasation portals but also CSC programming sites.Entities:
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Year: 2021 PMID： 34911937 PMCID： PMC8674234 DOI： 10.1038/s41467-021-27308-2
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919