Stem Cell Laboratory, Peter MacCallum Cancer Institute, St. Andrew's Place, East Melbourne VIC 3002, Australia
Address for correspondence: Paul J. Simmons, Stem Cell Laboratory, Peter MacCallum Cancer Institute, St. Andrew's Place, East Melbourne VIC 3002, Australia. Voice: 61 3 9656 3713; fax: 61 3 9656 3738.
p.simmons{at}pmci.unimelb.edu.au
Current data suggest that interplay between two classes of molecules
contributes to the regulation of hematopoiesis:
hematopoietic growth factors, which regulate the survival, proliferation,
and development of primitive hematopoietic cells and
cell adhesion molecules (CAMs), which are responsible for the localization
of hematopoiesis to the bone marrow (BM) and for mediating physical
association between developing hematopoietic cells and marrow
stromal tissue. A range of cell surface molecules representing
several CAM superfamilies including integrins, selectins, the
immunoglobulin gene superfamily and an emerging family of mucin-like
molecules (the sialomucins) are involved in supporting cell-cell
and cell-extracellular matrix (ECM) interactions between primitive
hematopoietic cells and the stromal cell-mediated hematopoietic
microenvironment (HM) of the bone marrow. There is abundant
evidence in non-hematopoietic tissues that CAMs are signalling
molecules which participate in a range of signal transduction
events important not only for regulating cell adhesion and motility,
but also for cell growth and survival. Although the signalling
functions of CAMs have not been studied extensively in primitive
hematopoietic progenitors (HPCs), extrapolation from burgeoning
data in other systems is consistent with the hypothesis that
hematopoiesis within the BM is regulated by interaction between
signals generated locally by CAMs and those elicited by cytokines.
Evidence in support of this notion was initially provided by
studies on normal HPCs demonstrating cross-talk between members
of the integrin superfamily and cytokine receptors. In this
article we review recent reports that mucin-like molecules are
also signalling molecules on primitive hematopoietic cells and
that the signals they deliver potently inhibit hematopoiesis.
