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Prepublished online as a Blood First Edition Paper on May 29, 2003; DOI 10.1182/blood-2002-10-3190.
Submitted October 22, 2002
Accepted May 16, 2003
Transforming growth factor- 1 downregulates expression of chemokine stromal cell-derived factor-1: functional consequences in cell migration and adhesion
Natalia Wright, Teresa Lain de Lera, Carelia Garcia-Moruja, Rosa Lillo, Felix Garcia-Sanchez, Antonio Caruz, and Joaquin Teixido*
Department of Immunology, Centro de Investigaciones Biologicas, Madrid, Spain
Department of Experimental Biology, University of Jaen, Jaen, Spain
Histocompatibility and Molecular Biology Laboratory, Centro de Transfusion de la Comunidad de Madrid, Madrid, Spain
* Corresponding author; email: joaquint{at}cib.csic.es.
The chemokine stromal cell-derived factor-1 (SDF-1) is expressed by bone marrow (BM) stromal cells and plays key roles in BM cell migration. Modulation of its expression could affect the migratory capacity of cells trafficking the BM, such as hematopoietic progenitor and leukaemic cells. Transforming growth factor- 1 (TGF-1) is present in the BM environment, and constitutes a pivotal molecule controlling BM cell proliferation and differentiation. We have used the BM stromal cell line MS-5 as a model to investigate whether SDF-1 expression constitutes a target for TGF-1 regulation, and its functional consequences. We show here that TGF-1 downregulates SDF-1 expression, both at mRNA level, involving a decrease in transcriptional efficiency, and at protein level, as detected in lysates and supernatants from MS-5 cells. Reduction of SDF-1 in supernatants from TGF-1-treated MS-5 cells correlated with decreased, SDF-1-dependent, chemotactic and transendothelial migratory responses of the BM model cell lines NCI-H929 and Mo7e, as compared with their response to supernatants from untreated MS-5 cells. In addition, supernatants from TGF-1-exposed MS-5 cells had a substantially lower efficiency in promoting integrin  41-mediated adhesion of NCI-H929 and Mo7e cells to sVCAM-1 and CS-1/fibronectin than their untreated counterparts. Moreover, human cord blood CD34+ hematopoietic progenitor cells displayed SDF-1-dependent reduced responses in chemotaxis, transendothelial migration and upregulation of adhesion to sVCAM-1 when supernatants from TGF-1-treated MS-5 cells were used, as compared to supernatants from untreated cells. These data indicate that TGF-1-controlled reduction in SDF-1 expression influences BM cell migration and adhesion, which could affect the motility of cells trafficking the bone marrow.
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