The role of osteopontin expression in melanoma progression

Abstract

It was shown that osteopontin (OPN), a glycophosphoprotein, plays divergent roles in cancer progression. In addition to multiple intra-and extracellular functions, it facilitates migration of tumor cells, has crucial role in cell adhesion and is associated with increased metastasis formation. In previous studies, we performed global gene-expression profiling on a series of primary melanoma samples and found that OPN was significantly overexpressed in ulcerated melanomas. The major purpose of this study was to define OPN expression in primary melanomas with differing biological behaviours. OPN mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in primary melanoma tissues. Immunohistochemistry was performed using a tissue microarray. Cox regression tests were used for survival analysis. Greater than 50% of the tissues exhibited high protein expression that was significantly associated with tumor thickness and metastasis. OPN mRNA expression was significantly increased in thicker melanomas and lesions with an ulcerated surface. Increased expression was primarily detected in advanced-stage tumors. A multivariate Cox regression analysis revealed that high OPN expression, tumor thickness, and metastasis were significantly associated with reduced relapse-free survival. In summary, high OPN mRNA and protein expression were associated with a less favourable clinical outcome of primary melanoma patients. We determined that OPN is a significant predictive factor for the survival of primary melanoma patients. Based on our and others data the high expression of OPN may have a crucial stimulatory role in tumor progression and metastasis formation, thus, have been proposed as potential targets for cancer diagnosis and therapy.3

Human osteopontin: Potential clinical applications in cancer (Review)

“…A study on patients with pancreatic ductal adenocarcinoma (PDAC) demonstrated that serum levels of OPN are elevated with advanced tumour grades (44). Elevated OPN levels have also been strongly associated with increased stage, grade and tumour size in melanoma patients (52). In early stage non-small cell lung cancer (NSCLC) patients high OPN plasma levels were observed which were reduced after surgical tumour resection.…”

Expression and Characterization of Membrane-Type 4 Matrix Metalloproteinase (MT4-MMP) and its Different Forms in Melanoma

“…This was due to the lack of osteopontin cleavage in the MT4-MMP -/-mice [7]. Osteopontin is a glycoprotein in the ECM with versatile functions in tumor progression, including the enhancement of tumor cell migration [33][34][35]. Hence, increased MT4-MMP activity could result in increased migratory potential in tumors due to osteopontin cleavage.…”

The role of integrins in TGFβ activation in the tumour stroma

“…Thus, increased osteopontin correlates with increased metastasis and often poor survival in multiple types of cancer including laryngeal squamous cell carcinoma (Chen et al 2015), melanoma (Kiss et al 2015), nasopharyngeal carcinoma (Hou et al 2015) and breast cancer (Xu et al 2015). Lenga et al (2008) reported that osteopontin was required for TGFβ1 transdifferentiation of cardiac fibroblasts to myofibroblasts, whereas Weber et al (2015) provided evidence that osteopontin induced bone-marrow-derived mesenchymal suppressor cells to become myofibroblasts.…”