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Supplementary Methods and Materials, Figure Legends 1-5 from 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

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posted on 2023-03-30, 19:14 authored by Antonella Zucchetto, Dania Benedetti, Claudio Tripodo, Riccardo Bomben, Michele Dal Bo, Daniela Marconi, Fleur Bossi, Debora Lorenzon, Massimo Degan, Francesca Maria Rossi, Davide Rossi, Pietro Bulian, Vito Franco, Giovanni Del Poeta, Silvia Deaglio, Gianluca Gaidano, Francesco Tedesco, Fabio Malavasi, Valter Gattei
Supplementary Methods and Materials, Figure Legends 1-5 from 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

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ARTICLE 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]

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    Cancer Research

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    Cell Death And SenescenceIntercellular interactions in apoptosisCell SignalingCell-cell interactionsComputational MethodsGene expression profilingHematological CancersLeukemiasImmunologyCytokinesTumor MicroenvironmentTumor-stromal cell interactions

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