Differential osteopontin expression in lung cancer
Introduction
Lung cancer is one of the most prevalent and lethal cancers among men in Japan and is classified into two histologic types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in terms of cell origin of the tumor. Its clinical features are dependent on the histologic types because each type of lung cancer appears to have specific tumor biology. Patients with early stage NSCLC are usually subjected to surgery. However, even after curative surgery, a quarter of these patients die within five years after diagnosis established. SCLC has poor prognosis despite combined chemo-radiotherapy because it metastasizes to systemic organs very rapidly. Recent advances in molecular biology have identified specific genetic alterations in tumorigenesis of various hisological types of lung cancer. For instance, K-ras oncogene is occasionally mutated in NSCLC [1], [2], [3], [4], while both p53 tumor suppressor gene and 3p are frequently deleted and/or mutated in SCLC [5]. However, our understanding of genetic alteration specific for histology of lung cancer is inadequate to overcome its dismal prognosis. To make an impact on the curability of lung cancer, we need to identify some of the specific molecules involved in tumorigenesis and progression, and apply it to the development of novel diagnostic and therapeutic approaches.
Osteopontin (OPN) is a multifunctional protein that is involved in bone mineralization, cell adhesion, migration, and transformation [6], [7], [8]. It is expressed in various cells including tumor cells and macrophages. OPN expression has been linked to tumorigenesis and metastasis in several experimental animal models and human cancers [9], [10], [11], [12], [13], [14], [15], [16]. Chambers et al. [14] have previously reported that OPN was expressed in lung cancer tissues and revealed a significant association between OPN-immunopositivity of the tumor and patient survival. However, little is known about OPN expression and its regulation in various histologic types of lung cancer. Transformation of normal fibroblasts with Ras oncogene has been documented to induce OPN expression [17], [18], [19]. Interestingly, Ras activation is observed predominantly in NSCLC, but rarely in SCLC [20], [21], [22]. Based on these findings, we hypothesized that OPN expression may differ among the two major histologic types of lung cancer. In this study, we first investigated the expression of OPN in NSCLC and SCLC tissues and then sought the correlation of OPN expression and Ras activation in the major histologic types of lung cancers. We also discussed the potential roles of OPN in the development of each histologic type of lung cancer.
Section snippets
Study population
The subjects enrolled in this study consisted of 16 squamous cell carcinoma (SCC, 15 male and one female), 24 adenocarcinoma (AD, 15 male and nine female) and 18 small cell lung cancer (SCLC, 15 male and three female) cases with a mean age of 64 years. There were 11, 14 and 17 smokers among the SCC, AD, and SCLC patients, respectively.
Tumor specimens and cell lines
Fifty lung cancer tissues including 40 NSCLC (16 SCC and 24 AD) and 10 SCLC were obtained by surgical resection at Juntendo University and Kanagawa Cancer Center.
Immunohistochemical staining of OPN in lung cancer tissues
We examined OPN expression in tumor tissues from 16 SCC, 24 AD and 18 SCLC cases. The representative findings for immunostaining of OPN are shown in Fig. 1. The immunoreactivities of OPN were remarkable in the tumor cells of SCC (Fig. 1A) and AD (Fig. 1C) in comparison with in those of SCLC (Fig. 1E). Some of the macrophages adjacent to the tumor cells of SCC (Fig. 1B) and AD (Fig. 1D) were also positive. The positive-staining for OPN was exhibited within cytoplasm in both the tumor cells and
Discussion
In this study, we revealed that OPN was preferentially expressed in tumor cells and macrophages in NSCLC tissues, but rarely in SCLC by immunohistochemical analysis. In addition, we examined not only protein expression but also mRNA expression among the lung cancer cell lines with Northern blotting to confirm the production of OPN from NSCLC cells. As expected, OPN mRNA expression was observed exclusively among the NSCLC cell lines, H322 and HL460, but not in the SCLC cell line, H69 cells,
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Role of osteopontin in lung cancer evolution and heterogeneity
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2015, European Journal of Pharmaceutics and BiopharmaceuticsCitation Excerpt :According to previous studies, OPN is overexpressed in various cancers [20] such as colon [21], breast [22], gastrointestinal, and liver cancers [23]. In particular, OPN is also overexpressed in NSCLC [3]. Thus, targeting OPN and down-regulation of its signaling pathway could represent a novel therapeutic approach for lung cancer treatment.
Osteopontin is associated with decreased apoptosis and αv integrin expression in lung adenocarcinoma
2014, Acta HistochemicaCitation Excerpt :There are several reports on the role of OPN in lung carcinoma progression however, the results are somehow contradictory and difficult to compare. Zhang et al. (2001) showed predominant OPN expression in NSCLC compared to small cell lung cancer, with higher OPN expression in SCC compared to AC. Higher levels of OPN have been shown to correlate with higher grade (Jin et al., 2012; Wang et al., 2012), higher clinical stage, lymph node metastasis (Hu et al., 2005; Jin et al., 2012; Wang et al., 2012), and patient's survival (Schneider et al., 2004; Boldrini et al., 2005; Donati et al., 2005).
Osteopontin combined with CD44v6, a novel prognostic biomarker in non-small cell lung cancer undergoing curative resection
2013, Annals of Thoracic Surgery