Integrin alphavbeta3, alpha5beta1 Effects on Cell Proliferation and Migration in Human Osteosarcoma

Kang, Hyun Guy; Kim, Han Soo; Kim, Kap Joong; Kim, Jun Hyuk; Seoul, So Mi; Oh, Joo Han; Lee, Sang Hoon; Choi, Sun Jong

Abstract

BACKGROUND
We investigate the influence of cell surface adhesion receptor integrin alphavbeta3, alpha5beta1 contributes to proliferation and migration of tumor cell in osteosarcoma for carves out a new treatment model by regulation of integrin roles in human osteosarcoma.
MATERIALS AND METHODS
We performed proliferation assay, total 11 cell lines including 7 osteosarcoma cell lines established from patients and 4 osteosarcoma standard cell lines. Murine monoclonal anti-alpha5beta1 and anti-alphavbeta3 (Chemicon International Inc. Temecula, CA) were used for growth inhibition assays. We also performed cell motility assay by using the Boyden chamber to evaluate the effect of integrin mediated cell migration. We used the HOS standard osteosarcoma cell lines and each separates contained serum free media with mouse IgG1 negative control antibody, anti-alpha5beta1 antibody and anti-alphavbeta3 antibody.
RESULTS
Proliferation of cells decreased significantly in 10 out of 11 cell lines when blocking with alphavbeta3 or alpha5beta1 respectively. Blocking with anti-alphavbeta3 antibody decreased significantly tumor cell proliferation in 10 cell lines. Among the 10 cell lines, 7 cell lines showed significantly more decrease of proliferation with anti-alphavbeta3 antibody than with anti-alpha5beta1antibody. Blocking with anti-alpha5beta1 antibody decreased significantly tumor cell proliferation in 10 cell lines. Among the 10 cell lines, 3 cell lines showed significantly more decrease of proliferation with anti-alpha5beta1 antibody than with anti-alphavbeta3 antibody. Including statistically not significant 2 cell lines the growth inhibition of osteosarcoma cell lines was more obvious (10 out of 11) in blocking with anti-alphavbeta3 antibody. The migration of cells was significantly decreased when blocked with anti-alpha5beta1 antibody and anti-alphavbeta3 antibody.
CONCLUSION
Under the based on the integrin alphavbeta3, alpha5 beta1 are central role on proliferation and migration of osteosarcoma cells, we could be more approach to new therapeutic endeavors with antibody to integrin alphavbeta3, alpha5beta1 molecular target of osteosarcoma.