Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner

Phillips, Reneé; Helbig, Karla J.; Hoek, Kylie H. Van der; Seth, Devanshi; Beard, Michael R.

doi:10.3748/wjg.v18.i26.3389

Cited by 29 publications

(21 citation statements)

References 34 publications

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“…1E), indicating that HCV-infection does not induce the formation of OPN splice variants. In contrast, recent studies have shown the formation of two splice variants of OPN in HCC [48]. This could be due to different cell types and the source of HCC tissue samples used in those studies.…”

Section: Discussionmentioning

confidence: 81%

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Role of Hepatitis C Virus Induced Osteopontin in Epithelial to Mesenchymal Transition, Migration and Invasion of Hepatocytes

et al. 2014

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Osteopontin (OPN) is a secreted phosphoprotein which has been linked to tumor progression and metastasis in a variety of cancers including hepatocellular carcinoma (HCC). Previous studies have shown that OPN is upregulated during liver injury and inflammation. However, the role of OPN in hepatitis C virus (HCV)-induced liver disease pathogenesis is not known. In this study, we determined the induction of OPN, and then investigated the effect of secreted forms of OPN in epithelial to mesenchymal transition (EMT), migration and invasion of hepatocytes. We show the induction of OPN mRNA and protein expression by HCV-infection. Our results also demonstrate the processing of precursor OPN (75 kDa) into 55 kDa, 42 kDa and 36 kDa forms of OPN in HCV-infected cells. Furthermore, we show the binding of secreted OPN to integrin αVβ3 and CD44 at the cell surface, leading to the activation of downstream cellular kinases such as focal adhesion kinase (FAK), Src, and Akt. Importantly, our results show the reduced expression of epithelial marker (E-cadherin) and induction of mesenchymal marker (N-cadherin) in HCV-infected cells. We also show the migration and invasion of HCV-infected cells using wound healing assay and matrigel coated Boyden chamber. In addition, we demonstrate the activation of above EMT markers, and the critical players involved in OPN-mediated cell signaling cascade using primary human hepatocytes infected with Japanese fulminant hepatitis (JFH)-1 HCV. Taken together, these studies suggest a potential role of OPN in inducing chronic liver disease and HCC associated with chronic HCV infection.

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Section: Discussionmentioning

confidence: 81%

“…Full-length OPN is composed of about 314 amino acids and there are also functionally important cleaved products and occasional splice variants [24], [38], [48]. In HCV-infected hepatoma cells, we could observe only full-length OPN mRNA (Fig.…”

Section: Discussionmentioning

confidence: 99%

Role of Hepatitis C Virus Induced Osteopontin in Epithelial to Mesenchymal Transition, Migration and Invasion of Hepatocytes

et al. 2014

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“…By utilizing more sensitive machines and methods, low abundance proteins that change with cancer development can be found and may be more directly related to the cancer. Using such methods, proteins such as peroxiredoxin 3 (Ai et al, 2006; Chen et al, 2010b; Guo et al, 2007; Li et al, 2008; Lu et al, 2010; Qiao et al, 2012; Song et al, 2009; Wang, 2007; Yue et al, 2007) and osteopontin have been identified as potential markers of HCC (Abu El Makarem et al, 2011; Chen et al, 2010a; Chen et al, 2011; Kim et al, 2006; Lin et al, 2011; Phillips et al, 2012; Qin and Tang, 2004; Shang et al, 2012; Tang et al, 2004; Ye et al, 2003; Zekri et al, 2011). While these markers have been shown to be elevated in other cancers, they may still have great value in the early detection of liver cancer (Chahed et al, 2008; Lehtonen et al, 2004; McAllister et al, 2008; Mirza et al, 2008; Park et al, 2008; Park et al, 2007; Reiniger et al, 2007; Schremmer et al, 2007; Tigrani and Weydert, 2007; Tuck et al, 2007; Whiteaker et al, 2007).…”

Section: Proteomic Identification Of Biomarkers Of Liver Cancermentioning

confidence: 99%

Glycosylation and Liver Cancer

Mehta

Herrera

Block

2015

Advances in Cancer Research

117

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Liver cancer is the 5th most common cancer, but the 2nd leading cause of cancer death, in the world, with more than 700,000 fatalities annually. The major etiology of liver cancer is infection with an hepatotropic virus such as hepatitis B virus (HBV) or hepatitis C virus infection (HCV). While chronic viral infection remains the main cause of liver disease and risk of HCC, rates of non –viral associated HCC are occurring at an alarmingly increasing rate. Like many cancers, survival rates are closely associated with time of detection. If HCC is caught early, survival rates can be as high as 50%. Regrettably, most cases of HCC are caught late where survival rates can be as low as 2–7%. Thus, there has been great interest in discovering serum biomarkers that could be used to identify those with HCC. To this end, many groups have examined the N-linked glycans to identify changes that occur with HCC. As the liver secretes the vast majority of proteins into the serum, this has often been a starting point for study. In serum, alterations in core fucosylation, outer-arm fucosylation, increased sialylation and glycan branching have been observed in patients with HCC. Similar findings have been found directly in HCC tissue suggesting that these glycan changes may play a role in tumor formation and development.

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“…Up-regulation of cell proliferation is associated with down-regulation of p27 and p21 and up-regulation of cyclin D1 [81]. Osteopontin plays role in the proliferation of HCC through interaction with the cell surface receptor CD44 [82] and is considered the key mediator for vasculogenic mimicry [83]. Baxinteracting factor is over-expressed in HCC and correlates with shortened survival [84].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Primary and Metastatic Tumours of the Liver: Expanding Scope of Morphological and Immunohistochemical Details in the Biopsy

Štrumfa¹,

Vilmanis²,

Vanags³

et al. 2012

Liver Biopsy - Indications, Procedures, Results

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Osteopontin increases hepatocellular carcinoma cell growth in a CD44 dependant manner

Abstract: This study demonstrates that OPN plays a significant role in the proliferation of HCC through interaction with the cell surface receptor CD44. Modulation of this interaction could represent a novel strategy for the control of HCC.

Cited by 29 publications

References 34 publications

Role of Hepatitis C Virus Induced Osteopontin in Epithelial to Mesenchymal Transition, Migration and Invasion of Hepatocytes

Role of Hepatitis C Virus Induced Osteopontin in Epithelial to Mesenchymal Transition, Migration and Invasion of Hepatocytes

Glycosylation and Liver Cancer

Primary and Metastatic Tumours of the Liver: Expanding Scope of Morphological and Immunohistochemical Details in the Biopsy

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