Bone sialoprotein mediates human endothelial cell attachment and migration and promotes angiogenesis

Akeila Bellahcène, Karine Bonjean, Berthold Fohr, Neal S. Fedarko, Frank A. Robey, Marian F. Young, Larry W. Fisher, Vincent Castronovo

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in sites of biomineralization. Recently, we demonstrated that BSP is strongly upregulated in osteotropic cancers and particularly those that exhibit microcalcifications. BSP contains an Arg-Gly-Asp (RGD) motif found in other adhesive molecules that interact with cellular integrins. In bone, BSP has been shown to mediate the attachment of osteoblasts and osteoclasts via α(v)β3 integrin receptors. Ligands for α(v)β3 integrin are considered to play a central role during angiogenesis. Therefore, we used human umbilical vein endothelial cells (HUVECs) to study the potential role of BSP in angiogenesis. We found that purified eukaryotic recombinant human BSP (rhBSP) is able to promote both adhesion and chemotactic migration of HUVECs in a dose-dependent manner. These interactions involve HUVEC α(v)β3 integrin receptors and the RGD domain of BSP. Indeed, HUVECs attach to a recombinant BSP fragment containing the RGD domain; whereas this response is not observed with the same fragment in which RGD has been mutated to Lys-Ala- Glu (KAE). A cyclic RGD BSP peptide inhibits both adhesion and migration of HUVECs to rhBSP. Moreover, anti-α(v)β3 but not anti-α(v)β3 monoclonal antibodies also prevent BSP-mediated adhesion and migration of HUVECs. We observed that both rhBSP and the RGD BSP recombinant fragment stimulated ongoing angiogenesis on the chorioallantoic chick membrane assay. BSP angiogenic activity was inhibited by anti-α(v)β3 antibody, and the KAE BSP fragment was inactive. Our findings represent the first report implicating BSP in angiogenesis. BSP could play a critical role in angiogenesis associated with bone formation and with tumor growth and metastatic dissemination.

Original languageEnglish (US)
Pages (from-to)885-891
Number of pages7
JournalCirculation research
Issue number8
StatePublished - Apr 28 2000
Externally publishedYes


  • Angiogenesis
  • Bone sialoprotein
  • Integrins

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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