摘要:

In the hemopoietic system, interactions between stem cells and components of the bone marrow microenvironment play a pivotal role in blood cell proliferation and differentiation. Among the adhesion molecules, the integrins of the β1-subfamily are known to direct cell-cell and cell-matrix interactions and evidence has been provided that CD34-positive stem cells bind either to the bone marrow stroma or to the extracellular matrix proteins through the β1-integrins. It seems that changes in their expression pattern or signalling function are likely to reflect disturbances at the hemopoietic bone marrow microenvironmental level. Any alteration of their biological functions makes them attractive candidates for playing decisive roles in the leukemic processes. In this view, β1-integrins have been recognized to mediate those cellular interactions and migrations that are important in the biology of leukemia. In this paper we review some aspects of the role played by β1-integrins, especially VLA-4 and VLA-5, in adult acute lymphoblastic leukemia in relation with the expression rate of the stem cell antigen C

ISSN:0001-5792    

DOI:10.1159/000203660

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Cell surface expression of adhesion molecules in B-cell chronic lymphocytic leukemia (B-CLL) may determine the patterns of dissemination and infiltration. B-CLL cells express high levels of CD44, but expression of the leucocyte integrins was low or absent, while expression of VLA-4 is high. Most cases examined expressed no detectable ICAM-1, but some cases demonstrated levels of up to 30%. Levels of L-selectin were also variable, and expression could be induced/enhanced in vitro by incubation with cytokines such as IL-4, interferon-α and interferon-γ. B-CLL cells bound normally to vascular endothelium, but binding to IL-1-activated endothelium was significantly lower than that of normal peripheral blood lymphocytes. Cytokine enhancement of L-selectin expression was not accompanied by changes in binding to vascular endothelium. Patterns of adhesion molecule expression and their regulation by cytokines may underly some of the clinical features of this diseas

ISSN:0001-5792    

DOI:10.1159/000203661

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Most non-Hodgkin’s lymphomas (NHLs) express a number of different adhesion receptors. A large body of evidence indicates that these adhesion receptors not only regulate normal lymphocyte trafficking but also play a pivotal role in the dissemination of NHL. Thus, cutaneous lymphocyte antigen, α4β7, αEβ7, and L-selectin, which mediate the tissue-specific positioning of normal lymphocytes in the skin, mucosa, epithelium and lymph nodes, respectively, are selectively expressed on lymphomas localized at these sites. Furthermore, expression of CD44, a family of adhesion receptors with pleiotropic effects on tumor behavior, is related to lymphoma aggressiveness and dissemination. Taken together, these findings offer a framework for the understanding of tumor dissemination in NHL. In view of the similarities between lymphocyte behavior and the metastatic behavior of solid tumors, these insights might contribute to the understanding of the basic mechanisms underlying tumor metastasis in non-lymphoid t

ISSN:0001-5792    

DOI:10.1159/000203662

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The neoplastic plasma cells of multiple myeloma differ from normal plasma cells and other B-cell malignancies by an almost exclusive homing to the bone marrow microenvironment which clearly provides the appropriate support, both physical and cytokine, to mediate clonal proliferation and terminal differentiation. Cellular adhesion molecules are involved in the homing of malignant plasma cells to the bone marrow, the production of growth factors and the recirculation of these tumour cells in the advanced stages of disease. Neoplastic plasma cells express H-CAM (CD44), VLA-4 (CD49d/CD29), ICAM-1 (CD54), N-CAM (CD56) and LFA-3 (CD58). In addition VLA-5 (CD49e/ CD29) expression seems to be related to cells with less proliferative potential and more potential for paraprotein production. In addition there are fundamental changes in the bone marrow stroma of patients with multiple myeloma including altered composition of the extracellular matrix, increased growth capability of the cellular elements and increased synthesis of interleukin-6 and interleukin-3, which are features postulated to localise and promote growth of the circulating neoplastic progenitors in the bone marrow. However, the evidence to date does not fully explain the inter-relationship of the clonal B cells and the bone marrow stroma in patients with myeloma, including factors which trigger and facilitate the extravasation and recirculation of neoplastic plasma cells as seen in advanced disease.

ISSN:0001-5792    

DOI:10.1159/000203663

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Peripheral blood (PB) mobilization of hematopoietic progenitors, presently regarded as an alternative source of cells intended for autologous or allogeneic bone marrow (BM) transplantation, supports a role for cytokines in the regulated adhesion of hematopoietic compartments to the BM microenvironment. Two major consequences might result from cytokine-induced rearrangements of adhesive interactions within the hematopoietic tissue, both potentially relevant for clinical purposes of PB grafts. The first one, arising from abrogated adhesion of hematopoietic stem cells to their microenvironmental ‘niche’, which is critical for the maintenance of cell cycle quiescence and endurability, might result in some impairment of the long-term repopulating potential of PB grafts. The second and possibly more harmful one is due to the inability of the cytokine to distinguish between normal and transformed cells, and would likely result in graft contamination by tumor cells, increasing the metastasizing potential of hematological malignancies and solid tum

ISSN:0001-5792    

DOI:10.1159/000203664

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Investigations of the homing of transplanted hemopoietic cells into preconditioned recipients have in most studies been referable to parameters that determine engraftment. The principles, however, that govern their early traffic into the host’s blood and tissues have remained much less explored. Early studies and experiments from our own laboratory suggest that intravenously administered hemopoietic cells, including progenitors, are not selectively taken up by bone marrow, as they are distributed widely in several tissues (liver, lung, kidney, spleen, bone marrow). As the hemopoietic cells are later on found almost exclusively in the bone marrow (and spleen in the mouse), the data argue for either preferential retention in these tissues or just only preferential survival and proliferation. Our recent studies showing modulation of cells lodged to the bone marrow, before proliferation ensues (i.e. 3 h after infusion), would favor preferential retainment and/or survival of these cells within the bone marrow. Furthermore we established that the VLA4/VCAM-1 adhesion pathway plays a significant role in this process, thus defining VCAM-1 as the dominant bone marrow endothelial addressin in hemopoietic cell homing. Since homing likely represents a cascade of adhesive interactions between hemopoietic cells and bone marrow stroma and/or its extracellular matrix, other adhesion pathways are likely to be involved and remain to be defined. Finally, our data on mobilization of hemopoietic progenitors from normal individuals, induced by blocking the VLA4/VCAM-1 adhesion pathway, suggest that the molecular pathways involved in homing are also of importance in governing hemopoietic progenitor cell trafficking in and out of the bone marro

ISSN:0001-5792    

DOI:10.1159/000203665

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A cascade of signaling events directs and regulates the trafficking, homing and activation of T lymphocytes after allogeneic transplantation. These adhesion receptors include selectins, integrins and adhesion molecules of the immunoglobulin superfamily. Tissue-specific homing receptors direct the tissue-specific trafficking of T lymphocytes. When T cells encounter their antigen(s) presented by MHC molecules on APC, the antigen-specific signal mediated through the T-cell receptor (TCR) needs to be accompanied by additional costimulatory signals for complete T-cell activation to occur. The costimulatory signal determines the outcome of the first signal generated through the TCR, leading to either complete activation, partial activation or to a long-lasting state of antigen-specific unresponsiveness, termed anergy. Complete activation of T cells results in IL-2R (CD25) receptor expression, IL-2 production and T-cell proliferation.

ISSN:0001-5792    

DOI:10.1159/000203666

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Adhesion molecules and adhesive interactions play a critical role in the process of hemostasis. A vascular rent requires a patch, and this patch must be provided from constituents of the cellular and fluid phases of flowing blood, constituents that must not interfere with this flow under unperturbed conditions. Platelets, the cellular elements of the patch, are inert until they encounter conditions that trigger their activation. In response to injury they undergo a rapid and dramatic change both in shape and in their surface characteristics, a change that allows them to become both the nidus and the stimulus for the precipitation of a meshwork of fibrin. The interactions between platelets and exposed collagen in the damaged vessel wall, plasma and platelet von Willebrand factor, and plasma and platelet fibrinogen can all be considered ‘adhesive interactions

ISSN:0001-5792    

DOI:10.1159/000203667

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203668

出版商:S. Karger AG    

年代:1997

数据来源: Karger