avb3 expression correlates with the metastatic potential of human osteosarcoma cells.

DUAN, XIAOPING; JIA, SHU-FANG; ZHOU, ZHICHAO; BOLONTRADE, MARCELA F.; KLEINERMAN, EUGENIE S.

Toronto, CA

Simposio; 94to Encuentro Anual. American Association for Cancer Research (AACR).; 2003

American Association for Cancer Research (AACR).

Tumor metastasis involves many stage-specific adhesion interactions. The expression of adhesion molecules such as ávâ3, has been associated with the metastatic potential of tumor cells. We developed a series of human osteosarcoma cell lines from SAOS-parental cells (LM2, LM3, LM4, LM5, LM6, and LM7) with progressively increasing potential to form lung metastases in nude mice following i.v. injection. SAOS-parental cells rarely form lung metastases after 10 months. By contrast the injection of LM7 cells results in numerous large visible metastases (median:200)by week 10. The purpose of this study was to determine whether ávâ3 expression correlated with metastatic potential. ávâ3 expression was quantified using flow cytometry and immunohistochemistry. ávâ3 was detected on 29%, 34%, 72%, and 86% of SAOS-parental, LM3, LM5, and LM7 cells respectively. LM7 cell adhesion to vitronectin decreased after treatment with Echistatin, an RGD containing peptide antagonist of ávâ3. Furthermore, the percentage of LM7 cells expressing ávâ3 decreased by 50% following incubation with Echistatin. These data indicate, osteosarcoma cells adhere to vitronectin by an RGD-dependent mechanism involving ávâ3 and that the integrin ávâ3 may play a role in the metastatic potential of osteosarcoma cells. ávâ3 may therefore represent a potential new target for therapy.