Focal adhesion protein abnormalities in myelodysplastic
mesenchymal stromal cells
Carmen Mariana Aanei
, Florin Zugun Eloae
, Pascale Flandrin-Gresta
, Eugen Carasevici
, Denis Guyotat
, Lydia Campos
Laboratoire Hématologie, CHU de Saint-Etienne, 42055, Saint-Etienne, France
Department of Immunology, Gr. T. Popa University of Medicine and Pharmacy, 700115, Iasi, Romania
Service Hématologie Clinique, Institut de Cancérologie de la Loire, 42270, Saint-Priest-en-Jarez, France
CNRS UMR 5239, Université de Lyon, 42023, Saint-Etienne, France
ARTICLE INFORMATION ABSTRACT
Received 17 April 2011
Revised version received 7 August 2011
Accepted 9 August 2011
Available online 16 August 2011
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
], and HSP90α/β 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
HSP90α/β formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y
HSP90α/β 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 HSP90α/β client
protein, these results suggest the utility of HSP90α/β inhibition as a target for adjuvant therapy for
© 2011 Elsevier Inc. All rights reserved.
Myelodysplastic syndromes (MDS) are clonal disorders of haema-
topoietic stem cells (HSCs) characterised by ineffective haematopoi-
esis that manifest clinically as anaemia, neutropoenia, and/or
thrombocytopoenia and increase the risk of transformation to
acute myeloid leukaemia. In MDS, the bone marrow (BM)
microenvironment is responsible for the intramedullary apoptosis
of HPCs, and this abnormal function appears to be dependent on
close cellular contact rather than on the release of soluble factors .
The BM microenvironment is also responsible for the selection of
neoplastic haematopoietic clone(s) that are resistant to apoptosis
and express factors promoting proliferation and migration .
Mesenchymal stromal cells (MSCs) are key components of the
haematopoietic microenvironment, and several studies have dem-
onstrated morphological and functional changes in these cells in
EXPERIMENTAL CELL RESEARCH 317 (2011) 2616– 2629
⁎ Corresponding author at: Laboratoire Hématologie, CHU de Saint-Etienne, 42055, Saint-Etienne, France. Fax: +33 38 66 18 201.
E-mail address: firstname.lastname@example.org (C.M. Aanei).
0014-4827/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
Available online at www.sciencedirect.com