ISSN:0001-5792    

DOI:10.1159/000203650

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203651

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203652

出版商:S. Karger AG    

年代:1997

数据来源: Karger

ISSN:0001-5792    

DOI:10.1159/000203653

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Blood cells developing in the bone marrow exhibit adhesive interactions with stromal reticular cells and specialized macrophages, and with several defined components of the extracellular matrix. Receptors that are known to participate in these interactions include certain integrins, selectins, members of the immunoglobulin superfamily, and CD44, and this list may be expected to grow. Specific inhibitors of some integrins and of CD44 have been shown to disrupt hemopoiesis in vitro; thus the function of adhesive receptors appears critical to blood cell development. The capacity of such receptors to transmit signals through the plasma membrane suggests that they regulate not just the physical interactions of hemopoietic cells, but also the responses of the cells to their environment.

ISSN:0001-5792    

DOI:10.1159/000203654

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The growth and differentiation of hematopoietic stem cells are highly dependent on regulatory molecules produced by stromal cells of the marrow environment. Evidence has accumulated over the past years which shows that adhesive receptors on hematopoietic cells and their ligands on stromal cells and extracellular matrix play a crucial role in these interactions. Integrins of the β1 family, mostly VLA-4 and VLA-5, are the best characterized and have been identified on committed progenitor cells of the hematopoietic hierarchy as well as on more primitive stem cells defined by their long-term repopulating capacity assayed in vitro as well as in vivo. Functional assays demonstrate that most progenitor cells efficiently bind to ECM components through β1 integrins and lineage- and maturation stage-specific differences have been described. Evidence exists on the direct control of late erythroid differentiation by VLA-4, but whether or not the triggering of β1 integrins is critically required for hematopoietic stem cell functioning at more immature steps is unclear. Many other integrin and non-integrin receptors involved in adhesive interactions are expressed on hematopoietic progenitor cells and tightly regulated during differentiation but their function is still controversial. Our main purpose in this review is to describe recent advances in the knowledge of integrin expression on hematopoietic progrenitor cells in both mouse and man. The emerging importance of the synergy between integrins and cytokine signalling pathways in the regulation of hematopoietic differentiation will also be discuss

ISSN:0001-5792    

DOI:10.1159/000203655

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The process of hematopoiesis is dependent on discrete cell-cell and cell-matrix interactions which are tightly regulated by expression of adhesion molecules. L-selectin, an adhesion protein best known for regulating leukocyte attachment to endothelium, is characteristically expressed on the earliest hematopoietic progenitor cells. Ligands for L-selectin have been extensively characterized on endothelial cells. We recently identified a ligand for L-selectin expressed on the human hematopoietic progenitor cell line KG1a. This molecule is an integral membrane glycoprotein which is structurally different from all ligands previously described. We hypothesize that this molecule may mediate L-selectin-specific adhesive interactions during hematopoiesis. This article discusses the biology of L-selectin and its ligands, and reviews our current understanding of the structure and distribution of the L-selectin ligand expressed on hematopoietic cells.

ISSN:0001-5792    

DOI:10.1159/000203656

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

The metastatic spread of cancer is a complex and multistep process characterized by a number of biological steps which include the hematogenous and lymphatic arrest and adhesion of circulating tumor cells in the vascular bed, invasion of tumor cells through the basement membrane, and growth of new tumor colonies in the organ parenchyma. In this brief review we describe the role of platelets, the hemostatic system, adhesive proteins and their putative receptors in the hematogenous dissemination of cancer. The major adhesive proteins postulated to play a role in tumor arrest in the vascular bed are thrombospondin-1 (TSP-1), laminin, fibronectin and hyaluronan-proteoglycans. The major tumor and vascular receptors mediating these adhesive interactions are the CSVTCG-specific TSP-1 receptor, the 67-kD laminin receptor, the αvβ3 vitronectin/TSP-1 /fibronectin receptor, and CD44 hyaluronan receptor. The discovery of the involvement of these adhesive proteins and receptors in the metastatic spread of cancer as well as components of the hemostatic system offers unique opportunities for the development of antimetastasis therapies for the treatment of cance

ISSN:0001-5792    

DOI:10.1159/000203657

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Hematopoiesis takes place in close contact with the marrow microenvironment. Normal progenitors adhere through a variety of receptors to stroma and extracellular matrix components, including fibronectin. Adhesion through integrins to fibronectin may not only serve to anchor progenitors to the microenvironment but also to directly alter the proliferative behavior of normal hematopoietic progenitors. Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell. At the molecular level, CML is characterized by the BCR/ABL gene rearrangement which encodes for the oncoprotein, p210bcr-abl. Presence of the p210bcr-abl tyrosine kinase is necessary and sufficient for the malignant transformation of hematopoietic cells. Clinically, CML is characterized by an abnormal, premature release of primitive progenitors and precursors in the blood and by the continuous proliferation of the malignant progenitor population. In vitro, CML progenitors fail to adhere to or be regulated by marrow stroma. Since CML progenitors express similar numbers of integrin adhesion receptors as normal progenitors, functional rather than quantitative differences of these receptors on CML progenitors may be responsible for the abnormal circulation and proliferation of the malignant clone. In this manuscript we will review the role of integrin adhesion receptors present on normal hematopoietic progenitors in the regulation of their proliferation and discuss signal transduction mechanisms that may be responsible for these effects. We will also discuss the integrin defect in CML which may be caused by the presence of the oncoprotein, P210bcr-abl, and may explain the abnormal trafficking and proliferation observed in CML.

ISSN:0001-5792    

DOI:10.1159/000203658

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

A variety of adhesion receptors are expressed on the blast cells in patients with acute myelogenous leukemia. The panel of receptors expressed demonstrates heterogeneity just as there is morphologic, histochemical, cytogenetic, and molecular genetic variation between various cases of acute myelogenous leukemia. The adhesion receptors expressed contain representatives of all the main classes of adhesion receptors, but often there is no correlation of the adhesion receptor phenotype with the morphologic or clinical features of acute myelogenous leukemia. These receptors function in interactions of myelogenous leukemia blasts with the cellular and matrix components of the marrow microenvironment, and there is evidence that they are involved in blast release from marrow and in homing of blasts to extrameduilary sites. Evidence is starting to accumulate suggesting that adhesive interactions may influence the proliferation and survival of leukemic cells, but the precise role that these molecules play in the generation and sustenance of the leukemic state remains undetermined.

ISSN:0001-5792    

DOI:10.1159/000203659

出版商:S. Karger AG    

年代:1997

数据来源: Karger