Mitochondrial dsRNA from B-ALL cells stimulates mesenchymal stromal cells to become cancer-associated fibroblasts.

ABSTRACT:

Abstract

Cancer-associated fibroblasts (CAFs) arising from bone marrow-derived mesenchymal stromal cells (MSCs) are prominent in B-cell precursor acute lymphoblastic leukemia (B-ALL). We have previously shown that CAF formation is triggered by exposure to reactive oxygen species-inducing chemotherapy and that CAFs support chemoresistance by donating mitochondria to the cancer cells through tunneling nanotubes. In the present study, we show that exposure of MSCs to ALL cell lines, patient-derived xenografts, and primary cells or their conditioned media can also trigger CAF formation. Using bulk RNA sequencing in cell lines, we show that the MSC to CAF transition is accompanied by a robust interferon pathway response, and we have validated this finding in primary cells. Using confoca

SUBMITTER: Burt RJ 

PROVIDER: S-EPMC11570786 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature