Osteopontin Expression and Serum Levels in Metastatic Uveal Melanoma: A Pilot Study

Kadkol, Shrihari S.; Lin, Amy; Barak, Vivian; Kalickman, Inna; Leach, Lu; Valyi‐Nagy, Klara; Majumdar, Dibyen; Setty, Suman; Maniotis, Andrew J.; Folberg, Robert; Pe’er, Jacob

doi:10.1167/iovs.05-0422

Cited by 61 publications

(54 citation statements)

References 35 publications

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“…Previous studies have suggested that increased serum osteopontin levels, one of the ligands for integrin avb3, correlates with melanoma metastasis and that integrin signaling has an important role in tumor progression (Dome et al, 2005;Zhou et al, 2005;Kadkol et al, 2006). Quantitative PCR analysis revealed that expression of integrin b3 and osteopontin was downregulated in the endoglin shRNA cells (Figures 5d and e).…”

Section: Resultsmentioning

confidence: 73%

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Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

et al. 2010

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Tumor cell plasticity enables certain types of highly malignant tumor cells to dedifferentiate and engage a plastic multipotent embryonic-like phenotype, which enables them to 'adapt' during tumor progression and escape conventional therapeutic strategies. This plastic phenotype of aggressive cancer cells enables them to express endothelial cell-specific markers and form tubelike structures, a phenotype that has been linked to aggressive behavior and poor prognosis. We demonstrate here that the transforming growth factor (TGF)-b coreceptor endoglin, an endothelial cell marker, is expressed by tumor cells and its expression correlates with tumor cell plasticity in two types of human cancer, Ewing sarcoma and melanoma. Moreover, endoglin expression was significantly associated with worse survival of Ewing sarcoma patients. Endoglin knockdown in tumor cells interferes with tumor cell plasticity and reduces invasiveness and anchorage-independent growth in vitro. Ewing sarcoma and melanoma cells with reduced endoglin levels showed reduced tumor growth in vivo. Mechanistically, we provide evidence that endoglin, while interfering with TGF-b signaling, is required for efficient bone morphogenetic protein, integrin, focal adhesion kinase and phosphoinositide-3-kinase signaling in order to maintain tumor cell plasticity. The present study delineates an important role of endoglin in tumor cell plasticity and progression of aggressive tumors.

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Section: Resultsmentioning

confidence: 73%

“…In addition, expression of integrin avb3 and osteopontin is increased in aggressive, highly metastatic cancer cells (Dome et al, 2005;Kadkol et al, 2006). Our results suggest that depletion of endoglin interferes with the activity of the FAK and PI3K pathways.…”

Section: Role Of Endoglin In Tumor Cell Plasticity E Pardali Et Almentioning

confidence: 62%

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

et al. 2010

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“…32 LMCD1 is a GATA transcription factor inhibitor that regulates migration and differentiation of mesenchymal cells. 33 Various individual biomarkers have been suggested for prognostication in uveal melanoma, including nibrin, 17 autotaxin, 34 osteopontin, 35 and TIMP3. 36 However, our findings here indicate that the simultaneous measurement of expression of several highly discriminating genes provides superior prognostic accuracy compared with individual biomarkers.…”

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confidence: 99%

An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

Onken

Worley

Tuscan

et al. 2010

The Journal of Molecular Diagnostics

295

275

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Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance , earlier intervention for metastasis , and stratification for entry into clinical trials of adjuvant therapy. Here , we migrate the expression profile from a hybridization-based microarray platform to a robust , clinically practical , PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples , including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples , even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma , and it provides a proof of principle for the development of similar assays for other cancers.

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“…A recent study showed that tissue sections of primary uveal melanomas lacking looping VM patterns either did not stain for OPN or exhibited weak, diffuse staining. In primary melanomas containing looping VM patterns, strong OPN staining was detected in the tumor periphery where patterns were located (Kadkol et al 2006). Another study suggested that increased expression of OPN by decreased levels of hsa-mir-299-5p (a miRNA) played a critical role in enhancing proliferation, tumorigenicity and the ability to display VM of the spheroid-forming cells of breast cancer cells (Shevde et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous report demonstrated that hypoxic inducible factor-1α, matrix metalloproteinase (MMP)-2, and MMP-9 were important for HCC cells to form VM . A smattering of plot studies have shown that osteopontin (OPN), an oncogenic protein that has been clinically correlated with increased tumor burden and adverse prognosis in patients with tumor metastasis, might be associated with VM in melanoma and breast cancer (Kadkol et al 2006;Shevde et al 2010). However, it is not known whether OPN plays an important role in regulating the ability of HCC cells to display VM.…”

mentioning

confidence: 99%

Osteopontin as a Key Mediator for Vasculogenic Mimicry in Hepatocellular Carcinoma

Liu

et al. 2011

Tohoku J. Exp. Med.

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Osteopontin (OPN) is overexpressed in a variety of cancers including hepatocellular carcinoma (HCC), and is likely involved in the process of vasculogenic mimicry (VM) in some tumor cells. In this study, we explored whether OPN plays a role for VM in HCC. Metastatic MHCC97-H human HCC cells and nonmetastatic Hep3B human HCC cells were compared for their abilities to establish VM. Three dimensionalculture assays showed that MHCC97-H cells but not Hep3B cells were able to form the chord-like structure that represents VM. Real-time RT-PCR arrays were used to detect gene expression profiles of the two HCC cell lines in three-dimensional culture. PCR array analyses revealed the increased expression of OPN in MHCC97-H cells forming VM compared with Hep3B cells. Small interfering RNA was employed to investigate whether OPN knockdown could influence VM, and the expression of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator (uPA) in MHCC97-H cells. OPN knockdown resulted in a significant decrease in the ability of MHCC97-H cells to form VM, which was accompanied by the down-regulation of MMP-2 and uPA expression. Furthermore, human HCC tissue samples were studied by immunohistochemistry to analyze the correlations between VM and the expression of OPN, MMP-2 and uPA. There existed significant positive correlations between VM and the expression of OPN, MMP-2 and uPA in HCC tissue samples. In conclusion, OPN is required for VM in HCC cells, and its action may be associated with activation of MMP-2 and uPA. OPN-targeted therapeutics may be useful for patients with advanced HCC.

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Osteopontin Expression and Serum Levels in Metastatic Uveal Melanoma: A Pilot Study

Abstract: Osteopontin is expressed diffusely in tissue sections of hepatic metastases from uveal melanoma, and increased serum osteopontin levels correlate with melanoma metastasis to the liver with high specificity and sensitivity.

Cited by 61 publications

References 35 publications

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

Critical role of endoglin in tumor cell plasticity of Ewing sarcoma and melanoma

An Accurate, Clinically Feasible Multi-Gene Expression Assay for Predicting Metastasis in Uveal Melanoma

Osteopontin as a Key Mediator for Vasculogenic Mimicry in Hepatocellular Carcinoma

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