CD38/CD31, the CCL3 and CCL4 Chemokines, and CD49d/Vascular Cell Adhesion Molecule-1 Are Interchained by Sequential Events Sustaining Chronic Lymphocytic Leukemia Cell Survival
Open Access
- 30 April 2009
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 69 (9), 4001-4009
- https://doi.org/10.1158/0008-5472.can-08-4173
Abstract
CD38 and CD49d are associated negative prognosticators in chronic lymphocytic leukemia (CLL). Despite evidence that both molecules are involved in interactions occurring between CLL and normal cells in the context of CLL-involved tissues, a functional link is still missing. Using gene expression profiles comparing CD38+CD49d+ versus CD38−CD49d− CLL cells, we showed overexpression of the CCL3 and CCL4 chemokines in cells from the former group. These chemokines were also up-regulated by CD38 signals in CLL; moreover, CCL3 was expressed by CLL cells from bone marrow biopsies (BMB) of CD38+CD49d+ but not CD38−CD49d− cases. High levels of CCR1 and, to a lesser extent, CCR5, the receptors for CCL3 and CCL4, were found in CLL-derived monocyte-macrophages. Consistently, CCL3 increased monocyte migration, and CD68+ macrophage infiltration was particularly high in BMB from CD38+CD49d+ CLL. Conditioned media from CCL3-stimulated macrophages induced endothelial cells to express vascular cell adhesion molecule-1 (VCAM-1), the CD49d ligand, likely through tumor necrosis factor α overproduction. These effects were apparent in BMB from CD38+CD49d+ CLL, where lymphoid infiltrates were characterized by a prominent meshwork of VCAM-1+ stromal/endothelial cells. Lastly, CD49d engagement by VCAM-1 transfectants increased viability of CD38+CD49d+ CLL cells. Altogether, CD38 and CD49d can be thought of as parts of a consecutive chain of events ultimately leading to improved survival of CLL cells. [Cancer Res 2009;69(9):4001–9]Other Versions
This publication has 48 references indexed in Scilit:
- CD49d expression is an independent risk factor of progressive disease in early stage chronic lymphocytic leukemiaHaematologica, 2008
- Decidual endothelial cells express surface-bound C1q as a molecular bridge between endovascular trophoblast and decidual endotheliumMolecular Immunology, 2008
- CD49d expression is an independent predictor of overall survival in patients with chronic lymphocytic leukaemia: a prognostic parameter with therapeutic potentialBritish Journal of Haematology, 2008
- Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemiaBlood, 2008
- Identification and Functional Characterization of the Hepatic Stellate Cell CD38 Cell Surface MoleculeThe American Journal of Pathology, 2007
- Comprehensive characterization of IGHV3-21–expressing B-cell chronic lymphocytic leukemia: an Italian multicenter studyBlood, 2006
- MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by α4β1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migrationBlood, 2006
- Magnitude of Stromal Hemangiogenesis Correlates with Histologic Subtype of Non–Hodgkin's LymphomaClinical Cancer Research, 2006
- Prognosis at diagnosis: integrating molecular biologic insights into clinical practice for patients with CLLBlood, 2004
- The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progressionBlood, 2003