Tunnelling nanotube-like intercellular projections are druggable mediators of cancer-niche crosstalk

ABSTRACT: Intercellular connections (ICCs) used by cancer cells to interact with their microenvironment have remained underexplored. Here we develop 3D co-culture organoids to investigate the role of ICCs in drug resistance. We create an animal-component-free bone marrow-mimicking Vitronectin-Alginate-Laminin (VAL) hydrogel, which exhibits viscoelastic properties representative of the human bone marrow (BM). VAL hydrogels support the culture of mesenchymal stroma cells (MSCs), the engraftment and expansion of patient-derived acute lymphoblastic leukaemia (ALL) cells and consequently form 3D co-culture organoids. We find that ALL therapies, such as, dexamethasone and BCL2 inhibition (using ABT-199), or their combination, induce the formation of tunnelling nanotube (TNT)-like projections between ALL c

SUBMITTER: Sean Hockney 

PROVIDER: S-SCDT-10_1038-S44319-026-00975-2 | biostudies-other |

REPOSITORIES: biostudies-other