Differences between healthy hematopoietic progenitors and leukemia cells with respect to CD44 mediated rolling versus adherence behavior on hyaluronic acid coated surfaces Maximilian Hanke a, b, c, d, 1 , Isabel Hoffmann d,1 , Christof Christophis a, b , Mario Schubert d , Van T. Hoang d , Abraham Zepeda-Moreno d, e , Natalia Baran d , Volker Eckstein d , Patrick Wuchter d , Axel Rosenhahn a, c, ** , Anthony D. Ho d, * a Institute of Functional Interfaces, Karlsruhe Institute of Technology, Karlsruhe, Germany b Applied Physical Chemistry, Heidelberg University, Heidelberg, Germany c Analytical Chemistry e Biointerfaces, Ruhr-University Bochum, Bochum, Germany d Department of Medicine V, Heidelberg University, Heidelberg, Germany e Child and Youth Cancer Research Institute, University Center for Health Sciences, University of Guadalajara, Guadalajara, Jalisco, Mexico article info Article history: Received 4 October 2013 Accepted 2 November 2013 Available online 22 November 2013 Keywords: CD44 Hyaluronic acid Hematopoietic progenitor cell Acute myeloid leukemia Shear stress Rolling abstract We previously demonstrated that leukemia cell lines expressing CD44 and hematopoietic progenitor cells (HPC) from umbilical cord blood (CB) showed rolling on hyaluronic acid (HA)-coated surfaces under physiological shear stress. In the present study, we quantitatively assessed the interaction of HPC derived from CB, mobilized peripheral blood (mPB) and bone marrow (BM) from healthy donors, as well as primary leukemia blasts from PB and BM of patients with acute myeloid leukemia (AML) with HA. We have demonstrated that HPC derived from healthy donors showed relative homogeneous rolling and adhesion to HA. In contrast, highly diverse behavioral patterns were found for leukemia blasts under identical conditions. The monoclonal CD44 antibody (clone BU52) abrogated the shear stress-induced rolling of HPC and leukemia blasts, confirming the significance of CD44 in this context. On the other hand, the immobile adhesion of leukemia blasts to the HA-coated surface was, in some cases, not or incompletely inhibited by BU52. The latter property was associated with non-responsiveness to induc- tion chemotherapy and subsequently poor clinical outcome. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction The mechanisms by which the adhesion molecule CD44 directs the locomotion of normal hematopoietic progenitor cells (HPC) versus leukemia blasts are extremely complex. CD44 has been re- ported to play an important role in the retention and homing of HPC in the bone marrow (BM) niche. Mobilization with G-CSF leads to CD44 cleavage in CD34 þ cells and subsequent detachment of these cells from stromal cells in mice. [1] An activating monoclonal CD44 antibody has been reported to reduce the leukemia repopu- lation of human AML transplanted in NOD/SCID mice. [2] With Hyaluronan (hyaluronic acid, HA), being a major binding partner for CD44, the importance of this extracellular matrix glycosamino- glycan is obvious [3]. Also as component of the stem cell niche and to maintain stem cell function HA plays an important role [4]. Furthermore, CD44 and HA have been shown to be essential for homing and engraftment of HPC into the bone marrow and spleen of NOD/SCID mice. [5] Different modes of glycosylation of CD44 influence the binding to HA [6e8]. Therefore, CD44 expression alone does not directly correlate with HA binding. This result is not surprising because both HA and CD44 are ubiquitous in the body. Thus, the force of adhesion depends on regulation of ligand ex- pressions, density of receptors, modes of glycosylation, and in- teractions with many other adhesion mechanisms that are not yet fully understood [9,10]. * Corresponding author. Department of Internal Medicine V, University of Hei- delberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Tel.: þ49 (0)6221 568000; fax: þ49 (0)6221 565813. ** Corresponding author. Department of Analytic Chemistry e Biointerfaces, Ruhr Universität Bochum, NC 4/27, Universitätsstr. 150, 44801 Bochum, Germany. Tel.: þ49 (0)234 32 24200; fax: þ49 (0)234 32 14420. E-mail addresses: axel.rosenhahn@rub.de (A. Rosenhahn), anthony_dick.ho@ urz.uni-heidelberg.de (A.D. Ho). 1 Shared first authorship. Contents lists available at ScienceDirect Biomaterials journal homepage: www.elsevier.com/locate/biomaterials 0142-9612/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.biomaterials.2013.11.011 Biomaterials 35 (2014) 1411e1419