THE EXTRACELLULAR-MATRIX OF THE HEMATOPOIETIC MICROENVIRONMENT

The bone marrow microenvironment plays an important role in promoting hematopoietic progenitor cell proliferation and differentiation and th e controlled egress of these developing hematopoietic cells. The estab lishment of long-term bone marrow cultures, which are thought to mimic hematopoiesis in vitro, and various stromal cell lines has greatly fa cilitated the analysis of the functions of this microenvironment. Extr acellular matrix (ECM) molecules of all three categories (collagens, p roteoglycans and glycoproteins) have been identified as part of this m icroenvironment and have been shown to be involved in different biolog ical functions such as cell adhesion and anti-adhesion. binding and pr esentation of various cytokines and regulation of cell growth. It is s uggested that these matrix molecules in combination with cytokines are crucial for compartmentalization of the bone marrow. Although many ce ll adhesion molecules have been characterized on the surface of hemato poietic 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 mic roenvironment 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 w ill certainly help towards a better understanding of these phenomena.