Mitogenic and adhesive effects of tenascin-C on human hematopoietic cells are mediated by various functional domains.
Matrix Biol
; 17(1): 47-63, 1998 Apr.
Article
em En
| MEDLINE
| ID: mdl-9628252
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
/
Tenascina
/
Mitógenos
Limite:
Humans
Idioma:
En
Revista:
Matrix Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Alemanha