Novel highly specific anti-periostin antibodies uncover the functional importance of the fascilin 1-1 domain and highlight preferential expression of periostin in aggressive breast cancer

3^rd World Congress on Women’s Health & Breast Cancer

October 03-05, 2016 London, UK

Parmjit Jat

UCL Institute of Neurology, UK

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

Periostin (POSTN), a secreted homodimeric protein that binds integrins �?±v�?²3, �?±v�?²35 and �?±6�?²4, was originally found to be expressed in fetal tissues and in the adult upon injury, particularly bone fractures, due to its role in remodeling and repair. Recently, it was found to be over-expressed in human breast cancer and a variety of other tumor types including head and neck squamous cell carcinoma, where its overexpression correlates with increased tumor invasion. Progress in studying its functional role in tumor pathogenesis has been hampered by the paucity of antibodies for its specific and sensitive detection. It has proven very difficult to obtain monoclonal antibodies (mAbs) against this highly conserved protein but we report here that combining infection of mice with lactate dehydrogenase elevating virus (LDV), a B cell activating arterivirus, with conjugation of human POSTN to ovalbumin as an immunogenic carrier, enabled us to develop 6 mAbs recognizing both human and mouse POSTN and inhibiting its binding to v3 integrin. Two of the mAbs, MPB4B1 and MPC5B4, were tested and found to inhibit POSTN-induced migration of human endothelial colony forming cells. All 6 mAbs recognized amino acids 136-51 (APSNEAWDNLDSDIRR) within the POSTN fascilin (FAS) 1-1 domain revealing the functional importance of this motif; this was further highlighted by the ability of aa 136-151 peptide to inhibit integrin-mediated cell migration. Immunohistochemistry using MPC5B4 indicated that breast tumor cell POSTN expression was a strong prognostic indicator, along with tumor size, lymph node and human epidermal growth factor receptor 2 (HER2) status.

Biography :

Email: p.jat@prion.ucl.ac.uk