Adhesion of osteosarcoma cells to the 70-kDa core region of thrombospondin-1 is mediated by the α4β1 integrin
Autor: | Stephan Decker, Frans van Valen, Peter Vischer |
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Rok vydání: | 2002 |
Předmět: |
Integrins
Integrin Receptors Lymphocyte Homing Biophysics Bone Neoplasms CD18 Integrin alpha4beta1 Biochemistry Thrombospondin 1 Cell Adhesion Tumor Cells Cultured Humans Cell adhesion Cell-substrate adhesion Molecular Biology Osteosarcoma biology Cell adhesion molecule Chemistry Cell Biology Adhesion Molecular biology Peptide Fragments Fibronectin biology.protein Neural cell adhesion molecule |
Zdroj: | Biochemical and Biophysical Research Communications. 293:86-92 |
ISSN: | 0006-291X |
Popis: | Thrombospondin-1 (TSP-1) is an extracellular glycoprotein that is involved in a variety of physiological processes such as tumor cell adhesion, invasion, and metastasis. It has been hypothesized that TSP-1 provides an adhesive matrix for osteosarcoma cells. Here we present data showing that TSP-1 can promote cell substrate adhesion to U2OS and SAOS cells through the alpha 4 beta 1 integrin. The dose-dependent adhesion to TSP-1 was inhibited by anti-integrin antibodies directed against the alpha 4 or beta 1 subunit, but not by control antibodies against other integrins. To localize the potential alpha 4 beta 1-binding site within the TSP-1 molecule, the protein was subjected to limited proteolysis with chymotrypsin in the absence of calcium. The stable 70-kDa core fragment produced under these conditions promoted alpha 4 beta 1-dependent osteosarcoma cell adhesion in a manner similar to that of the intact protein. Moreover adhesion experiments with neutralizing antibodies revealed that the adhesion was totally dependent on the alpha 4 beta 1 interaction. Further blocking experiments with potential inhibitory peptides revealed that the alpha 4 beta 1-mediated adhesion was not influenced by peptides containing the RGD sequence. Attachment to the 70-kDa fragment was strongly inhibited by the CS-1 peptide, which represents the most active recognition domain for alpha 4 beta 1 integrin in fibronectin. The present data provide evidence that TSP-1 contains an alpha 4 beta 1 integrin-binding site within the 70-kDa core region. |
Databáze: | OpenAIRE |
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