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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Serine Protease Inhibitor Kunitz-Type 2 Is Downregulated in Myelodysplastic Syndromes and Modulates Cell-Cell Adhesion

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Roversi, Fernanda Marconi [1] ; Lopes, Matheus Rodrigues [1] ; Machado-Neto, Joao Agostinho [1] ; Longhini, Ana Leda F. [1] ; Santos Duarte, Adriana da Silva [1] ; Baratti, Mariana Ozello [1] ; Palodetto, Bruna [1] ; Corrocher, Flavia Adolfo [1] ; Pericole, Fernando Vieira [1] ; Campos, Paula de Melo [1] ; Favaro, Patricia [1, 2] ; Traina, Fabiola [1, 2, 3] ; Olalla Saad, Sara Teresinha [1]
Total Authors: 13
[1] Univ Campinas Hemoctr Unicamp, Inst Nacl Ciencia & Tecnol Sangue, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil
[2] Univ Fed Sao Paulo, Dept Biol Sci, Diadema - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049 Ribeirao Preto - Brazil
Total Affiliations: 3
Document type: Journal article
Source: STEM CELLS AND DEVELOPMENT; v. 23, n. 10, p. 1109-1120, MAY 15 2014.
Web of Science Citations: 4

Myelodysplastic syndromes (MDS) are clonal disorders involving hematopoietic stem cells (HSC) characterized by ineffective hematopoiesis. In addition to HSC defects, a defective hematopoiesis supporting capacity of mesenchymal stromal cells (MSCs) in the microenvironment niche has been implicated in MDS pathophysiology. The interaction between the dysfunctional MSCs MDS and HSC regulates diverse adhesion-related processes, such as progenitor cell survival, proliferation, differentiation, and self-renewal. As previously reported, a microarray analysis identified serine protease inhibitor kunitz-type 2 (SPINT2), an inhibitor of hepatocyte growth factor (HGF) activation, to be downregulated in MSCs from MDS patients. To define the role of SPINT2 in MDS hematopoietic microenvironment, an analysis of the effect of SPINT2 silencing in MSCs was carried out. We herein reported significantly lower levels of SPINT2 whereas HGF was expressed at higher levels in MSCs from MDS patients compared with healthy controls. SPINT2 underexpression results in an increased expression, production, and secretion of HGF and stromal cell-derived factor 1 (SDF-1) by MSCs. An increased adhesion of normal HSC or malignant cells onto MSCs silenced for SPINT2 was also observed. The altered MSCs adhesion in SPINT2-knockdown cells was correlated with increased CD49b and CD49d expression and with a decrease in CD49e expression. Our results suggest that the SPINT2 underexpression in the MSC from MDS patients is probably involved in the adhesion of progenitors to the bone marrow niche, through an increased HGF and SDF-1 signaling pathway. (AU)

FAPESP's process: 11/22376-7 - Investigation deregulated pathways in myelodysplasia and acute leukemia from previous results obtained using microarray
Grantee:Fernanda Marconi Roversi
Support Opportunities: Scholarships in Brazil - Post-Doctoral