The extracellular matrix of the hematopoietic microenvironment

Abstract

The bone marrow microenvironment plays an important role in promoting hematopoietic progenitor cell proliferation and differentiation and the controlled egress of these developing hematopoietic cells. The establishment of long-term bone marrow cultures, which are thought to mimic hematopoiesis in vitro, and various stromal cell lines has greatly facilitated the analysis of the functions of this microenvironment. Extracellular matrix (ECM) molecules of all three categories (collagens, proteoglycans and glycoproteins) have been identified as part of this microenvironment and have been shown to be involved in different biological functions such as cell adhesion and anti-adhesion, binding and presentation of various cytokines and regulation of cell growth. It is suggested that these matrix molecules in combination with cytokines are crucial for compartmentalization of the bone marrow. Although many cell adhesion molecules have been characterized on the surface of hematopoietic progenitor cells, the nature of cellular receptors for the ECM components is less well defined. During leukemia, many immature blood cells are released from bone marrow, but it is not yet known whether these abnormalities in hematopoiesis are also caused by an altered microenvironment or altered composition of its extracellular matrix. The elucidation of the involvement of specific ECM-isoforms and as yet not characterized ECM components and their receptors in the bone marrow will certainly help towards a better understanding of these phenomena.

Protein-energy malnutrition halts hemopoietic progenitor cells in the G0/G1 cell cycle stage, thereby altering cell production rates

“…Cytokine-related stimulation allows the overexpression of this receptor. The abnormalities found in ECM components could alter the co-localization of the diverse growth factors and cytokines, which are required to modulate the growth and differentiation process of hematopoietic cells (12,28,35). This in turn may alter the cell-cell and cell-ECM interactions, thereby modifying the signaling pathways and leading to bone marrow hypoplasia with a depletion of progenitor hematopoietic populations and peripheral pancytopenia.…”

In silico subtraction approach reveals a close lineage relationship between follicular dendritic cells and BP3hi stromal cells isolated from SCID mice

“…3), known to control the availability of cytokines, chemokines and growth factors [29][30][31]. Indeed, by expressing collagens and fibronectin essential for assembling conduits, FDC may help to regulate the transport of low-molecular-weight proteins [32].…”

In vitro effects of native human acute myelogenous leukemia blasts on fibroblasts and osteoblasts

“…[3][4][5][6][7][8][9][10][11][12][13][15][16][17] The molecular bidirectional crosstalk with stromal cells appears to support AML blast proliferation, [3][4][5][6][7][8][9]16,20,22 and our own prior studies demonstrated that both fibroblast cell lines HFL1 and Hs27, the osteoblastic sarcoma cell lines Cal72 and SJSA-1 and normal osteoblasts 33,34 can increase AML blast proliferation as well as release of proangiogenic IL-8 by native human AML cells. Fibroblasts also have an additional antiapoptotic effect, 22 and this effect is observed both with Hs27 and HFL1 fibroblasts (Ryningen, unpublished).…”

“…5,6,14 -16 Thirdly, stromal cells produce extracellular matrix, e.g., different collagens, proteoglycans (e.g., chondroitin sulfate, heparan sulfate, dermatan sulfate), hyaluronan and glycoproteins like fibronectin, laminin and thrombospondin. 5,10,17 One function of these molecules is to bind growth factors and thereby create a local extracellular reservoir. 17 The stromal cells together with their matrix components thereby constitute an interacting network with AML cells.…”

“…5,10,17 One function of these molecules is to bind growth factors and thereby create a local extracellular reservoir. 17 The stromal cells together with their matrix components thereby constitute an interacting network with AML cells. 11,18 The proliferative capacity of in vitro cultured AML blasts varies between patients: spontaneous or autocrine in vitro proliferation is detected only for a subset of patients and associated with poor prognosis.…”