PMID- 31964707
OWN - NLM
STAT- MEDLINE
DCOM- 20210618
LR  - 20230829
IS  - 1477-9137 (Electronic)
IS  - 0021-9533 (Linking)
VI  - 133
IP  - 5
DP  - 2020 Mar 5
TI  - Genetic engineering of Hoxb8-immortalized hematopoietic progenitors - a potent 
      tool to study macrophage tissue migration.
LID - jcs236703 [pii]
LID - 10.1242/jcs.236703 [doi]
AB  - Tumor-associated macrophages (TAMs) are detrimental in most cancers. Controlling 
      their recruitment is thus potentially therapeutic. We previously found that TAMs 
      perform protease-dependent mesenchymal migration in cancer, while macrophages 
      perform amoeboid migration in other tissues. Inhibition of mesenchymal migration 
      correlates with decreased TAM infiltration and tumor growth, providing rationale 
      for a new cancer immunotherapy specifically targeting TAM motility. To identify 
      new effectors of mesenchymal migration, we produced ER-Hoxb8-immortalized 
      hematopoietic progenitors (cells with estrogen receptor-regulated Hoxb8 
      expression), which show unlimited proliferative ability in the presence of 
      estrogen. The functionality of macrophages differentiated from ER-Hoxb8 
      progenitors was compared to bone marrow-derived macrophages (BMDMs). They 
      polarized into M1- and M2-orientated macrophages, generated reactive oxygen 
      species (ROS), ingested particles, formed podosomes, degraded the extracellular 
      matrix, adopted amoeboid and mesenchymal migration in 3D, and infiltrated tumor 
      explants ex vivo using mesenchymal migration. We also used the CRISPR/Cas9 system 
      to disrupt gene expression of a known effector of mesenchymal migration, WASP 
      (also known as WAS), to provide a proof of concept. We observed impaired podosome 
      formation and mesenchymal migration capacity, thus recapitulating the phenotype 
      of BMDM isolated from Wasp-knockout mice. Thus, we validate the use of 
      ER-Hoxb8-immortalized macrophages as a potent tool to investigate macrophage 
      functionalities.
CI  - (c) 2020. Published by The Company of Biologists Ltd.
FAU - Accarias, Solene
AU  - Accarias S
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Sanchez, Thibaut
AU  - Sanchez T
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Labrousse, Arnaud
AU  - Labrousse A
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Ben-Neji, Myriam
AU  - Ben-Neji M
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Boyance, Aurelien
AU  - Boyance A
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Poincloux, Renaud
AU  - Poincloux R
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Maridonneau-Parini, Isabelle
AU  - Maridonneau-Parini I
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France.
FAU - Le Cabec, Veronique
AU  - Le Cabec V
AUID- ORCID: 0000-0002-0204-0976
AD  - Institut de Pharmacologie et Biologie Structurale, IPBS, Universite de Toulouse, 
      CNRS, UPS, Toulouse 31290, France veronique.le-cabec@ipbs.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200305
PL  - England
TA  - J Cell Sci
JT  - Journal of cell science
JID - 0052457
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Hoxb8 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Cell Movement/genetics
MH  - Genetic Engineering
MH  - *Hematopoietic Stem Cell Transplantation
MH  - Homeodomain Proteins/genetics
MH  - *Macrophages
MH  - Mice
OTO - NOTNLM
OT  - CRISPR/Cas9
OT  - Conditionally immortalized macrophages
OT  - ER-Hoxb8
OT  - Macrophage migration
COIS- Competing interestsThe authors declare no competing or financial interests.
EDAT- 2020/01/23 06:00
MHDA- 2021/06/22 06:00
CRDT- 2020/01/23 06:00
PHST- 2019/07/19 00:00 [received]
PHST- 2019/12/16 00:00 [accepted]
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/01/23 06:00 [entrez]
AID - jcs.236703 [pii]
AID - 10.1242/jcs.236703 [doi]
PST - epublish
SO  - J Cell Sci. 2020 Mar 5;133(5):jcs236703. doi: 10.1242/jcs.236703.