Evidence for differences in the mechanisms by which antibodies against CD44 promote adhesion of erythroid and granulopoietic progenitors to marrow stromal cells

Abstract

Summary.Adhesive interactions between haemopoietic progenitor cells and stromal elements involve a number of different molecules, some of which may be progenitorlineage-and stage-specific. CD44 is one such molecule, although little is known about the mechanism(s) by which it is involved. In this study, several anti-CD44 monoclonal antibodies (mAb) increased the adherence of clonogenic cells, without affecting the total number of types of progenitors recoverable from the adhesion cultures. All of these mAb recognized epitopes on the globular head of CD44. In contrast, two mAb that recognized other regions of CD44 reduced progenitor adhesion to stroma. The mechanism by which one of the anti-CD44 mAb (L178) enhanced progenitor adhesion did not involve CD44-crosslinking, and was independent of VLA-4-, VLA-5-or LFA-1-mediated interactions, Ca or Mg cations, or accessory cells. In addition, CD44 expression on both progenitors and stromal cells contributed to L178-enhanced progenitor adhesion. Baseline adherence of erythroid progenitors to stroma required tyrosine kinase activity, whereas that of granulopoietic progenitors did not. However, the increase in adhesion did require tyrosine kinase activation. Additional experiments suggested that enhanced adhesion of CFU-GM to stroma may also be adenylate cyclase-dependent. Taken together, the present studies indicate both similarities and differences in the mechanisms of CD44-mediated adhesion of erythroid and granulopoietic progenitors to stromal cells.

Kinetics of in vivo homing and recruitment into cycle of hematopoietic cells are organ-specific but CD44-independent

“…2 In vitro studies suggest that the strength of the interactions of hematopoietic cells with extracellular matrix proteins depends on transient activation signals stimulated by concomitant interactions of the hematopoietic cells with cytokines like GM-CSF and Steel factor (SF) 3 or certain costimulatory adhesion molecules like the ␤1-integrins, CD44 and ICAM-3. [4][5][6] Such activation signals peak between 15 min and 2 h after ligand binding and then decline, thereby providing a dynamic process of adhesion and detachment which facilitates the ability of hematopoietic cells to move through the type of stromal cell network that extends throughout the bone marrow cavity.…”

“…19 On the other the hand, we and others have demonstrated that antibodies against CD44 can affect the growth, differentiation and adhesion of normal and leukemic hematopoietic progenitors in vitro in different ways, depending on the epitope specificity of the anti-CD44 antibodies tested. 6,16,[20][21][22] Thus, it was of interest to further examine the role of CD44 in the homing and engraftment of normal bone marrow cells in a syngeneic setting using other strategies. To address this question we compared various parameters of in vitro and in vivo hematopoietic stem cell activity and transplant engraftment in normal mice and mice deficient in CD44 expression (CD44 Ϫ/Ϫ mice).…”

Metastasis suppressors in human benign prostate, intraepithelial neoplasia, and invasive cancer: their prospects as therapeutic agents

“…[58][59][60] CD44 spans the membrane, containing an extracellular, transmembrane, and cytoplasmic domain. 53,61 The N-terminal domain mediates the binding of CD44 to ECM proteins, such as hyaluronan, 53,62 osteopontin, 63 collagen, laminin, 64 and fibronectin. 65 The transmembrane domain is responsible for lymphocyte homing, while the carboxyl cytoplasmic domain is anchored to the actin cytoskeleton and is important in signal transduction and cell migration functions of CD44.…”

Neural Cell Adhesion Molecule Contributes to Hemopoiesis‐Supporting Capacity of Stromal Cell Lines

“…The FMS/PA6-P cells also expressed other surface molecules, such as Sca-1 [27], which functions as a regulator of hemopoietic progenitor cell proliferation, and VCAM-1 [39], ICAM-1 [40], and CD44 [41], which have been shown to mediate the interaction between hemopoietic cells and stromal cells. They play a critical role in normal hemopoiesis by providing signals to elicit the proliferation and differentiation of HSCs.…”

“…However, the FMS/PA6-P cell line reacted with anti-CD44, Sca-1, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and very late antigen 4 (VLA-4) mAbs (Fig. 1), which is characteristic of hemopoiesis-supporting stromal cells [27,[39][40][41][42]. Most interestingly, a high expression of molecules recognized by the anti-PA6 mAb was observed in FMS/PA6-P cells until approximately the 20th passage.…”