Perlecan in human bone marrow: a growth-factor-presenting, but anti-adhesive, extracellular matrix component for hematopoietic cells.
Human perlecan is a heparan sulfate proteoglycan with a large core protein of 467 kDa to which three glycosaminoglycan side chains are attached. It belongs to the heparan sulfate proteoglycan family which has been implicated in strong interactions between developing hematopoietic cells and their microenvironment in the bone marrow. Here we report that perlecan is highly expressed in the human bone marrow, as well as in long-term bone marrow cultures which are thought to mimic hematopoiesis in vitro. Expression of perlecan in this tissue was shown by Northern blotting of the 14-kb mRNA of the core protein and by immunofluorescence stainings. Functionally, perlecan shows a strong anti-adhesive effect on unfractionated bone marrow cells and on various hematopoietic cell lines, repelling the cells from the perlecan-coated area. In contrast, perlecan is adhesive for fibroblasts and endothelial cells. It is suggested that the anti-adhesive site is located within the core protein of perlecan since heparitinase-treated perlecan still shows the repellent effect. Although anti-adhesive for hematopoietic cells, perlecan is able to bind growth factors like granulocyte/macrophage-colony stimulating factor and present them to hematopoietic progenitor cells in a semi-solid colony assay. The functional role of a growth-factor-binding extracellular matrix component in the bone marrow microenvironment with anti-adhesive properties is uncertain but may be related to compartmentalization.
Klein
G
G
University Medical Clinic, Department of Internal Medicine II, Tübingen.
Conzelmann
S
S
Beck
S
S
Timpl
R
R
Müller
C A
CA
D000328:Adult; D000818:Animals; D001853:Bone Marrow / Q000737:chemistry*; D002448:Cell Adhesion; D003114:Colony-Forming Units Assay; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000502:physiology*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000737:chemistry; D009924:Organ Culture Techniques; D011485:Protein Binding; D011509:Proteoglycans / Q000502:physiology*; D012513:Sarcoma, Experimental / Q000737:chemistry
D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D009363:Neoplasm Proteins; D011509:Proteoglycans; C071927:perlecan