PMID- 34435622
OWN - NLM
STAT- MEDLINE
DCOM- 20211026
LR  - 20211026
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 134
IP  - 18
DP  - 2021 Sep 15
TI  - Analyzing normal and disrupted leukemic stem cell adhesion to bone marrow stromal 
      cells by single-molecule tracking nanoscopy.
LID - jcs258736 [pii]
LID - 10.1242/jcs.258736 [doi]
AB  - 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.
CI  - (c) 2021. Published by The Company of Biologists Ltd.
FAU - Gorshkova, Oksana
AU  - Gorshkova O
AUID- ORCID: 0000-0001-5735-2574
AD  - Centre de recherche en cancerologie de Marseille (CRCM), Centre national de la 
      recherche scientifique (CNRS), Institut national de la sante et de la recherche 
      medicale (Inserm), Institut Paoli-Calmettes (IPC), Aix-Marseille Universite, 
      F-13273 Marseille, France.
FAU - Cappai, Jessica
AU  - Cappai J
AD  - Centre de recherche en cancerologie de Marseille (CRCM), Centre national de la 
      recherche scientifique (CNRS), Institut national de la sante et de la recherche 
      medicale (Inserm), Institut Paoli-Calmettes (IPC), Aix-Marseille Universite, 
      F-13273 Marseille, France.
FAU - Maillot, Loriane
AU  - Maillot L
AUID- ORCID: 0000-0001-9936-2957
AD  - Laboratoire adhesion inflammation (LAI), Centre national de la recherche 
      scientifique (CNRS), Institut national de la sante et de la recherche medicale 
      (Inserm), Aix-Marseille Universite, F-13288 Marseille, France.
FAU - Serge, Arnauld
AU  - Serge A
AUID- ORCID: 0000-0003-4271-3706
AD  - Centre de recherche en cancerologie de Marseille (CRCM), Centre national de la 
      recherche scientifique (CNRS), Institut national de la sante et de la recherche 
      medicale (Inserm), Institut Paoli-Calmettes (IPC), Aix-Marseille Universite, 
      F-13273 Marseille, France.
AD  - Laboratoire adhesion inflammation (LAI), Centre national de la recherche 
      scientifique (CNRS), Institut national de la sante et de la recherche medicale 
      (Inserm), Aix-Marseille Universite, F-13288 Marseille, France.
LA  - eng
GR  - 713750/Marie Curie/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210927
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Cell Adhesion Molecules)
SB  - IM
MH  - Cell Adhesion
MH  - Cell Adhesion Molecules/genetics
MH  - *Mesenchymal Stem Cells
OTO - NOTNLM
OT  - Adhesion
OT  - Leukemic stem cell
OT  - Nanoscopy
OT  - Single-molecule tracking
OT  - Super-resolution microscopy
COIS- Competing interests The authors declare no competing or financial interests.
EDAT- 2021/08/27 06:00
MHDA- 2021/10/27 06:00
CRDT- 2021/08/26 09:00
PHST- 2021/04/01 00:00 [received]
PHST- 2021/08/02 00:00 [accepted]
PHST- 2021/08/27 06:00 [pubmed]
PHST- 2021/10/27 06:00 [medline]
PHST- 2021/08/26 09:00 [entrez]
AID - 271951 [pii]
AID - 10.1242/jcs.258736 [doi]
PST - ppublish
SO  - J Cell Sci. 2021 Sep 15;134(18):jcs258736. doi: 10.1242/jcs.258736. Epub 2021 Sep 
      27.