Osteopontin as potential biomarker and therapeutic target in gastric and liver cancers

Abstract

Gastric cancer and liver cancer are among the most common malignancies and the leading causes of death worldwide, due to late detection and high recurrence rates. Today, these cancers have a heavy socioeconomic burden, for which a full understanding of their pathophysiological features is warranted to search for promising biomarkers and therapeutic targets. Osteopontin (OPN) is overexpressed in most patients with gastric and liver cancers. Over the past decade, emerging evidence has revealed a correlation of OPN level and clinicopathological features and prognosis in gastric and liver cancers, indicating its potential as an independent prognostic indicator in such patients. Functional studies have verified the potential of OPN knockdown as a therapeutic approach in vitro and in vivo. Furthermore, OPN mediates multifaceted roles in the interaction between cancer cells and the tumor microenvironment, in which many details need further exploration. OPN signaling results in various functions, including prevention of apoptosis, modulation of angiogenesis, malfunction of tumor-associated macrophages, degradation of extracellular matrix, activation of phosphoinositide 3-kinase-Akt and nuclear factor-κB pathways, which lead to tumor formation and progression, particularly in gastric and liver cancers. This editorial aims to review recent findings on alteration in OPN expression and its clinicopathological associations with tumor progression, its potential as a therapeutic target, and putative mechanisms in gastric and liver cancers. Better understanding of the implications of OPN in tumorigenesis might facilitate development of therapeutic regimens to benefit patients with these deadly malignancies.

Keywords: Biomarker; Gastrointestinal cancer; Metastasis; Osteopontin; Prognosis.

Figure 1

Structural features of osteopontin isoforms. Three isoforms of osteopontin (OPN), OPN-a, OPN-b and OPN-c, are known. All of them possess identical domains [aspartate domain, arginine-glycine-aspartate domain, Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) domain, thrombin cleavage domain, calcium binding domain and heparin binding domain] that are linked together with various linkers. These isoforms distinguish themselves by having a variable length of the linker between signal peptide and aspartate domain. RGD: Arginine-glycine-aspartate.

Figure 2

Molecular mechanisms of osteopontin in gastrointestinal cancers. Osteopontin (OPN) signaling leads to gastrointestinal cancer growth and metastasis through activation of various pathways, including cell survival and proliferation, angiogenesis, and extracellular matrix (ECM) degradation. VEGF: Vascular endothelial growth factor; PI3-K: Phosphoinositide 3-kinase; COX-2: Cyclooxygenase-2; MAPK: Mitogen-activated protein kinase; NF: Nuclear factor; uPA: Urokinase-type plasminogen activator; MMP: Matrix metalloproteinase; ERM: Ezrin/radixin/moesin; Akt: Protein kinase B.