title: Neutralizing monoclonal antibody to periostin inhibits ovarian tumor growth and metastasis.
abstract: Periostin, an extracellular matrix protein, is reported to be overexpressed in a variety of human cancers and its functions seem to be linked to tumor metastasis. Our previous results show that engineered periostin overexpression promotes ovarian tumor growth and dissemination in vivo. In this study, we developed a neutralizing monoclonal antibody to periostin, named MZ-1, and investigated its effects on human ovarian tumor growth and metastasis. Our in vivo studies showed significant growth inhibition by MZ-1 on both subcutaneous and intraperitoneal (i.p.) tumors derived from the periostin-expressing ovarian cancer cell line A2780. In addition, MZ-1 treatment led to a reduction of the metastatic potential of these A2780 i.p. tumors. The in vivo antitumor effects of MZ-1 were linked to its specific inhibition of anchorage-independent growth and survival of periostin-expressing cells, as well as its neutralizing effects on periostin-induced cancer cell migration and invasion. The data suggest that blocking periostin expression may be a novel approach for treating the subset of invasive ovarian tumors that overexpress periostin protein.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, University of California-Los Angeles School of Medicine, Los Angeles, CA 90095, USA. MZhu@mednet.ucla.edu
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Romaine E
authors.initials: RE
authors.lastname: Saxton
authors.forename: Lillian
authors.initials: L
authors.lastname: Ramos
authors.forename: David D
authors.initials: DD
authors.lastname: Chang
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Karlan
authors.forename: Judith C
authors.initials: JC
authors.lastname: Gasson
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human