Premium
Osteopontin overexpression in breast cancer: Knowledge gained and possible implications for clinical management
Author(s) -
Tuck Alan B.,
Chambers Ann F.,
Allan Alison L.
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21520
Subject(s) - osteopontin , cd44 , cancer research , metastasis , urokinase receptor , breast cancer , angiogenesis , integrin , cancer , carcinogenesis , biology , cell adhesion , malignancy , matrix metalloproteinase , cell migration , cell , plasminogen activator , medicine , immunology , pathology , endocrinology , biochemistry
Abstract Osteopontin (OPN) is a secreted protein that is overexpressed in a number of human cancers, and has been associated with increased metastatic burden and poor prognosis in breast cancer patients. The OPN protein contains several conserved structural elements including heparin‐ and calcium‐binding domains, a thrombin‐cleavage site, a CD44 binding site, and two integrin‐binding sites. Experimental studies have shown that the ability of OPN to interact with a diverse range of factors, including cell surface receptors (integrins, CD44), secreted proteases (matrix metalloproteinases, urokinase plasminogen activator), and growth factor/receptor pathways (TGFα/EGFR, HGF/Met) is central to its role in malignancy. These complex signaling interactions can result in changes in gene expression, which ultimately lead to alterations in cell properties involved in malignancy such as adhesion, migration, invasion, enhanced tumor cell survival, tumor angiogenesis, and metastasis. Therefore, OPN is not merely associated with cancer, but rather it plays a multi‐faceted functional role via complex molecular cross‐talk with other factors. This review will focus on the role of OPN in breast cancer, in particular on the malignancy‐promoting aspects of OPN that may reveal opportunities for new approaches to the clinical management of breast cancer. J. Cell. Biochem. 102: 859–868, 2007. © 2007 Wiley‐Liss, Inc.