?ig-h3 promotes human osteosarcoma cells metastasis by interacting with integrin ?2?1 and activating PI3K signaling pathway.

ABSTRACT: Osteosarcoma, the most common primary bone tumor in children and young adolescents, is characterized by local invasion and distant metastasis. But the detailed mechanisms of osteosarcoma metastasis are not well known. In the present study, we found that ?ig-h3 promotes metastatic potential of human osteosarcoma cells in vitro and in vivo. Furthermore, ?ig-h3 co-localized with integrin ?2?1 in osteosarcoma cells. But ?ig-h3 did not change integrin ?2?1 expression in Saos-2 cells. Interaction of ?ig-h3 with integrin ?2?1 mediates metastasis of human osteosarcoma cells. The second FAS1 domain of ?ig-h3 but not the first FAS1 domain, the third FAS1 domain or the fourth FAS1 domain mediates human osteosarcoma cells metastasis, which is the ?2?1 integrin-interacting domain. We further demonstrated that PI3K/AKT signaling pathway is involved in ?ig-h3-induced human osteosarcoma cells metastasis process. Together, these results reveal ?ig-h3 enhances the metastasis potentials of human osteosarcoma cells via integrin ?2?1-mediated PI3K/AKT signal pathways. The discovery of ?ig-h3-mediated pathway helps us to understand the mechanism of human osteosarcoma metastasis and provides evidence for the possibility that ?ig-h3 can be a potential therapeutic target for osteosarcoma treatment.

SUBMITTER: Guo YS 

PROVIDER: S-EPMC3942417 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature