Analyzing normal and disrupted leukemic stem cell adhesion to bone marrow stromal cells by single-molecule tracking nanoscopy - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Cell Science Année : 2021

Analyzing normal and disrupted leukemic stem cell adhesion to bone marrow stromal cells by single-molecule tracking nanoscopy

Oksana Gorshkova
Loriane Maillot

Résumé

ABSTRACT Leukemic stem cells (LSCs) adhere to bone niches through adhesion molecules. These interactions, which are deeply reorganized in tumors, contribute to LSC resistance to chemotherapy and leukemia relapse. However, LSC adhesion mechanisms and potential therapeutic disruption using blocking antibodies remain largely unknown. Junctional adhesion molecule C (JAM-C, also known as JAM3) overexpression by LSCs correlates with increased leukemia severity, and thus constitutes a putative therapeutic target. Here, we took advantage of the ability of nanoscopy to detect single molecules with nanometric accuracy to characterize junctional adhesion molecule (JAM) dynamics at leuko-stromal contacts. Videonanoscopy trajectories were reconstructed using our dedicated multi-target tracing algorithm, pipelined with dual-color analyses (MTT2col). JAM-C expressed by LSCs engaged in transient interactions with JAM-B (also known as JAM2) expressed by stromal cells. JAM recruitment and colocalization at cell contacts were proportional to JAM-C level and reduced by a blocking anti-JAM-C antibody. MTT2col revealed, at single-molecule resolution, the ability of blocking antibodies to destabilize LSC binding to their niches, opening opportunities for disrupting LSC resistance mechanisms.

Dates et versions

hal-03560820 , version 1 (07-02-2022)

Identifiants

Citer

Oksana Gorshkova, Jessica Cappaï, Loriane Maillot, Arnauld Sergé. Analyzing normal and disrupted leukemic stem cell adhesion to bone marrow stromal cells by single-molecule tracking nanoscopy. Journal of Cell Science, 2021, 134 (18), ⟨10.1242/jcs.258736⟩. ⟨hal-03560820⟩
14 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More