کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10904527 1086607 2011 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Focal adhesion protein abnormalities in myelodysplastic mesenchymal stromal cells
چکیده انگلیسی
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 [Y397], 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 [Y397], and HSP90α/β formed nuclear molecular complexes. Increased expression of paxillin, pFAK [Y397], and 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 myelodysplasia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 317, Issue 18, 1 November 2011, Pages 2616-2629
نویسندگان
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