Inhibition of Breast Cancer Metastasis and Angiogenesis by Antiosteopontin mAb 1A12

Osteopontin (OPN) is associated with many diseases, and its role in tumor growth and metastasis has been studied in breast cancers. Previous studies have described anti-OPN antibodies that could inhibit tumor

Osteopontin （OPN） is associated with many diseases, and its role in tumor growth and metastasis has been studied in breast cancers. Previous studies have described anti-OPN antibodies that could inhibit tumor cell adhesion and invasion in vitro, but until now, there are no systematic studies on antitumor metastasis effects of anti-OPN antibodies in vivo. In the present study, we have raised an mouse anti-OPN monoclonal antibody 1A12, and constructed a humanized version of 1A12 （hu1A12）. We found that it was able to inhibit MDA-MB-43Ss breast cancer cell attachment, invasion, migration, and colony formation in soft agar. Furthermore, We find that OPN enhances the expression of VEGF through phosphorylation of AKT and ERK. In turn, OPN-induced VEGF activates PI3K/AKT and ERK1/2 pathway as a positive feedback signal. Blocking the feedback signal by anti- VEGF antibody,