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

Field, Sarah, Uyttenhove, Catherine, Stroobant, Vincent, Cheou, Paméla, Coutelier, Jean-Paul, Simpson, Peter T., Cummings, Margaret C., Saunus, Jodi M., Reid, Lynne E., Kutasovic, Jamie R., McNicol, Anne Marie, Kim, Ba Reun, Kim, Jae Ho, Lakhani, Sunil R., Neville, A. Munro, Van Snick, Jacques and Jat, Parmjit S. (2016) 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. International Journal of Cancer, 138 8: 1959-1970. doi:10.1002/ijc.29946


Author Field, Sarah
Uyttenhove, Catherine
Stroobant, Vincent
Cheou, Paméla
Coutelier, Jean-Paul
Simpson, Peter T.
Cummings, Margaret C.
Saunus, Jodi M.
Reid, Lynne E.
Kutasovic, Jamie R.
McNicol, Anne Marie
Kim, Ba Reun
Kim, Jae Ho
Lakhani, Sunil R.
Neville, A. Munro
Van Snick, Jacques
Jat, Parmjit S.
Title 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
Journal name International Journal of Cancer   Check publisher's open access policy
ISSN 0020-7136
1097-0215
Publication date 2016-04-01
Year available 2015
Sub-type Article (original research)
DOI 10.1002/ijc.29946
Open Access Status Not Open Access
Volume 138
Issue 8
Start page 1959
End page 1970
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2016
Language eng
Formatted abstract
Periostin (POSTN), a secreted homodimeric protein that binds integrins αvβ3, αvβ5 and α6β4, was originally found to be expressed in fetal tissues and in the adult upon injury particularly bone fractures due to its role in remodelling and repair. Recently it was found to be over-expressed in human breast cancer and a variety of other tumour types including head and neck squamous cell carcinoma, where its overexpression correlates with increased tumour invasion. Progress in studying its functional role in tumour 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 αvβ3 integrin. Two of the mAbs, MPB4B1 and MPC5B4, were tested and found to inhibit POSTN-induced migration of human endothelial colony forming cells. All six 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 tumour cell POSTN expression was a strong prognostic indicator, along with tumour size, lymph node, and human epidermal growth factor receptor 2 (HER2) status.
Keyword Periostin
FAS1-1 domain
Breast cancer
Extracellular matrix protein
Diagnostic markers
Monoclonal antibodies
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
School of Medicine Publications
 
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Created: Tue, 08 Dec 2015, 23:55:57 EST by Peter Simpson on behalf of UQ Centre for Clinical Research