Mitogenic and adhesive effects of tenascin-C on human hematopoietic cells are mediated by various functional domains.
In the adult organism, the extracellular matrix molecule tenascin-C is prominently expressed in the bone marrow. Bone marrow mononuclear cells can adhere to plastic-immobilized tenascin-C, and in the present study we have used bacterial expression proteins to map the domains of tenascin-C responsible for binding of hematopoietic cells. A strong binding site was found to be located within the fibrinogen-like domain, and this binding could be inhibited by heparin, suggesting interactions with membrane-bound heparan sulfate proteoglycans. A second strong binding site was identified within the fibronectin type III-like repeats 6-8, and was also inhibitable by heparin. Adhesion to both attachment sites could not be blocked by various anti-integrin antibodies. A third hematopoietic cell binding site is located in the fibronectin type III-like repeats 1-5, which harbor an RGD sequence in the third fibronectin type III-like repeat. Binding to this domain, however, seems to be RGD-independent, since RGD-containing peptides could not inhibit cell binding; the addition of heparin also did not block adhesion to this domain. Since contradictory results had been reported on a proliferative effect of soluble tenascin-C, we also analyzed its activity on hematopoietic cells. The heterogeneous bone marrow mononuclear cells show a striking proliferative response in the presence of tenascin-C which is concentration-dependent. This result indicates a strong mitogenic activity of tenascin-C on primary hematopoietic cells. Using recombinant fragments of human tenascin-C, we identified several mitogenic domains within the tenascin-C molecule. These adhesive and mitogenic effects of tenascin-C suggest a direct functional association with proliferation and differentiation of hematopoietic cells within the bone marrow microenvironment.
Seiffert
M
M
University Medical Clinic, Dept. II, Tübingen, Germany.
Beck
S C
SC
Schermutzki
F
F
Müller
C A
CA
Erickson
H P
HP
Klein
G
G
D001665:Binding Sites / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D010449:Peptide Mapping; D011994:Recombinant Proteins; D019063:Tenascin / Q000235:genetics / Q000494:pharmacology*
D008934:Mitogens; D011994:Recombinant Proteins; D019063:Tenascin; D006493:Heparin