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Title: Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells

Abstract

Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90{alpha}/{beta} client protein, these results suggest the utility of HSP90{alpha}/{beta} inhibition as a target for adjuvant therapy for myelodysplasia.

Authors:
 [1];  [2];  [3];  [1];  [3];  [2]
  1. Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi (Romania)
  2. Laboratoire Hematologie, CHU de Saint-Etienne, 42055, Saint-Etienne (France)
  3. Service Hematologie Clinique, Institut de Cancerologie de la Loire, 42270, Saint-Priest-en-Jarez (France)
Publication Date:
OSTI Identifier:
22212182
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 317; Journal Issue: 18; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGY; CELL PROLIFERATION; INHIBITION; NEOPLASMS; PROTEINS; THERAPY

Citation Formats

Aanei, Carmen Mariana, E-mail: caanei@yahoo.com, Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi, Eloae, Florin Zugun, Flandrin-Gresta, Pascale, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Tavernier, Emmanuelle, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Carasevici, Eugen, Guyotat, Denis, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Campos, Lydia, and CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells. United States: N. p., 2011. Web. doi:10.1016/J.YEXCR.2011.08.007.
Aanei, Carmen Mariana, E-mail: caanei@yahoo.com, Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi, Eloae, Florin Zugun, Flandrin-Gresta, Pascale, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Tavernier, Emmanuelle, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Carasevici, Eugen, Guyotat, Denis, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Campos, Lydia, & CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne. Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells. United States. https://doi.org/10.1016/J.YEXCR.2011.08.007
Aanei, Carmen Mariana, E-mail: caanei@yahoo.com, Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi, Eloae, Florin Zugun, Flandrin-Gresta, Pascale, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Tavernier, Emmanuelle, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Carasevici, Eugen, Guyotat, Denis, CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne, Campos, Lydia, and CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne. 2011. "Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells". United States. https://doi.org/10.1016/J.YEXCR.2011.08.007.
@article{osti_22212182,
title = {Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells},
author = {Aanei, Carmen Mariana, E-mail: caanei@yahoo.com and Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi and Eloae, Florin Zugun and Flandrin-Gresta, Pascale and CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne and Tavernier, Emmanuelle and CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne and Carasevici, Eugen and Guyotat, Denis and CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne and Campos, Lydia and CNRS UMR 5239, Universite de Lyon, 42023, Saint-Etienne},
abstractNote = {Direct cell-cell contact between haematopoietic progenitor cells (HPCs) and their cellular microenvironment is essential to maintain 'stemness'. In cancer biology, focal adhesion (FA) proteins are involved in survival signal transduction in a wide variety of human tumours. To define the role of FA proteins in the haematopoietic microenvironment of myelodysplastic syndromes (MDS), CD73-positive mesenchymal stromal cells (MSCs) were immunostained for paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and p130CAS, and analysed for reactivity, intensity and cellular localisation. Immunofluorescence microscopy allowed us to identify qualitative and quantitative differences, and subcellular localisation analysis revealed that in pathological MSCs, paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y{sup 397}], and HSP90{alpha}/{beta} and enhanced nuclear co-localisation of these proteins correlated with a consistent proliferative advantage in MSCs from patients with refractory anaemia with excess blasts (RAEB) and negatively impacted clonogenicity of HPCs. These results suggest that signalling via FA proteins could be implicated in HPC-MSC interactions. Further, because FAK is an HSP90{alpha}/{beta} client protein, these results suggest the utility of HSP90{alpha}/{beta} inhibition as a target for adjuvant therapy for myelodysplasia.},
doi = {10.1016/J.YEXCR.2011.08.007},
url = {https://www.osti.gov/biblio/22212182}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 18,
volume = 317,
place = {United States},
year = {Tue Nov 01 00:00:00 EDT 2011},
month = {Tue Nov 01 00:00:00 EDT 2011}
}