Osteopontin as a target for cancer therapy.
Osteopontin (OPN) is a glycophosphoprotein cytokine that has multiple functions. OPN is expressed and secreted by various cells, and has a role in cell adhesion, chemotaxis, prevention of apoptosis, invasion, migration and anchorage-independent growth of tumor cells. Extensive research has demonstrated the pivotal participation of OPN in the regulation of cell signaling which controls neoplastic and malignant transformation. The elevated expression of OPN has been observed in a variety of cancers. OPN has been linked with tumor metastasis and signifies a poor prognosis for the patient. This review details the mechanisms by which OPN facilitates these pathological events. It will also show that gaining an understanding of the mechanism of OPN's action at a cellular level has led to the development of a number of therapeutic strategies against the cytokine. These include inhibiting its expression, antagonizing cell surface receptor activation and blocking downstream cell signaling pathways. In addition to the potential of these therapies, serum levels of OPN could be used as a diagnostic and prognostic marker. The authors propose that with further research and development, osteopontin directed treatment could greatly enhance outcomes for cancer patients.
Johnston
Nicholas I F
NI
Centre for Cancer Research and Cell Biology, Queen's University, Belfast, United Kingdom.
Gunasekharan
Vignesh Kumar
VK
Ravindranath
Amod
A
O'Connell
Ciara
C
Johnston
Patrick G
PG
El-Tanani
Mohamed K
MK
D017209:Apoptosis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018919:Neovascularization, Physiologic; D053495:Osteopontin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000502:physiology; D014158:Transcription, Genetic
D011956:Receptors, Cell Surface; D053495:Osteopontin