Heat Shock Protein Expression in the Eye and in Uveal Melanoma

Missotten, Guy S.; Korver, Johanna G. Journe ́e-de; Wolff-Rouendaal, D. De; Keunen, J. E. E.; Schlingemann, Reinier O.; Jager, Martine J.

doi:10.1167/iovs.02-1038

Cited by 35 publications

(32 citation statements)

References 37 publications

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“…In uveal melanoma, a single previous study has reported expression of Hsp90, which was found to be expressed in 60% of cases; however, the average percentage of tumor cell staining reported was of 6% (29). In comparison with previous results, we showed a higher degree of positive staining in our uveal melanoma cases, with 68% of cases staining positive and an average of 50% of tumor cells stained.…”

Section: Discussioncontrasting

confidence: 66%

Immune Expression and Inhibition of Heat Shock Protein 90 in Uveal Melanoma

Faingold

Marshall

Antecka

et al. 2008

Clinical Cancer Research

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Purpose:To examine the immunohistochemical profile of heat shock protein 90 (Hsp90) in uveal melanoma and the cytotoxicity of an Hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in uveal melanoma cell lines. Experimental Design: Hsp90 expression was determined by immunohistochemistry in 44 paraffin-embedded sections of primary human uveal melanoma and in five uveal melanoma cell lines (92.1, OCM-1, MKT-BR, SP6.5, and UW-1). Sulforhodamine B^based proliferation assay was used to compare uveal melanoma cell growth with a range of concentrations of 17-AAG. Changes in cell migration, invasion, cell cycle fractions, and apoptotic activity were also evaluated. Expression of intracellular proteins was determined by Western blot analysis after 17-AAG exposure.Results: Immunohistochemical expression of Hsp90 was identified in 68% of the paraffinembedded sections and significantly associated with largest tumor dimension (P = 0.03). 17-AAG significantly reduced the proliferation rates of uveal melanoma cell lines, with concentrations of 100 to 0.1 Amol/L. 17-AAG also significantly reduced the migratory and invasive capabilities of uveal melanoma cell lines. Cell cycle analysis showed that 17-AAG induced accumulations of cells in G 1 . Caspase-3 protease activity analysis, a marker for apoptosis, showed a significant increase after drug exposure. The cytotoxic effect of 17-AAG was associated with decreased levels of phosphorylated Akt and cyclin-dependent kinase 4. Conclusions: The immunohistochemical expression of Hsp90 in uveal melanoma indicates worse prognosis.To the best of our knowledge, this is the first report showing the inhibitory effect on uveal melanoma cells using 17-AAG to target Hsp90. Therefore, Hsp90 may be used as a potential target for treatment of patients with uveal melanoma.

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Section: Discussioncontrasting

confidence: 66%

Immune Expression and Inhibition of Heat Shock Protein 90 in Uveal Melanoma

Faingold

Marshall

Antecka

et al. 2008

Clinical Cancer Research

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“…Similar studies using melanoma tissue have previously reported that hsp90 and hsp70 are expressed in a minority of tumour cells and that hsp90 shows nuclear localisation (Missotten et al 2003;Westekemper et al 2011), but the results from the present study are not in accordance with these earlier reports. Although a number of studies have shown that the expressions of hsp70 and hsp90 are up- regulated in melanoma tissue relative to melanocytic naevi or melanocytes (McCarthy et al 2008;Becker et al 2004;Deichmann et al 2004;Farkas et al 2003), to the best of our knowledge, this is the first report that the expressions of hsp90, hsp70, hsp60 and hsp40 proteins are increased in melanoma cells relative to neighbouring non-transformed cells.…”

Section: Discussioncontrasting

confidence: 90%

“…The validation of hsps as therapeutic targets is of particular importance because hsp inhibitors are currently being evaluated in the treatment of melanoma patients (STA-9090 in Metastatic Ocular Melanoma 2011). Studies to date have demonstrated that hsps play important roles in melanoma, but few clear relationships have been defined and conflicting data have been reported (McCarthy et al 2008;Missotten et al 2003;Faingold et al 2008;Ricaniadis et al 2001;Lazaris et al 1995). This present study reports a preliminary assessment of hsp expression in metastatic melanoma tumour tissue with respect to patient clinical parameters.…”

Section: Introductionmentioning

confidence: 88%

Hsps are up-regulated in melanoma tissue and correlate with patient clinical parameters

Shipp

Weide²,

Derhovanessian

et al. 2013

Cell Stress and Chaperones

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Heat shock proteins (hsps) have been studied in numerous cancer types, but a clear view of their clinical relevance in melanoma remains elusive. Therefore, the aim of this study was to investigate the expression of hsps in melanoma with respect to patient clinical parameters. Using Western immunoblotting, hsps 90, 70, 60, 40 and 32 were observed to be widely expressed in metastatic melanomas (n031), while immunofluorescence demonstrated that in the majority of samples these hsps, apart from hsp32, were increased in expression in melanoma cells compared with surrounding non-melanoma cells in situ (n08). Correlating hsp expression with patient clinical parameters indicated that greater hsp90 (P<0.02) and hsp40 (P<0.03) expression correlated with advanced stage (stage III Vs stage IV), while in the case of hsp40, this was additionally associated with reduced patient survival (P<0.05). In contrast, higher hsp32 expression was associated with improved patient survival (P<0.007). On the other hand, the expression of the other hsps did not correlate with any obtainable patient clinical parameters. This study provides further evidence for the importance of hsps in melanoma and for their use as therapeutic targets and biomarkers, but larger-scale follow-up studies are required to confirm these results.

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“…To date, its expression has been detected in breast, endometrial, ovarian, lung cancer, melanoma and others [10,[16][17][18][19][20][21][22][23][24]. In ovarian, prostate and gastric cancer, a high level of Hsp27 expression was associated with a poor clinical outcome [10].…”

Section: Discussionmentioning

confidence: 99%

Hsp-27 Expression in Invasive Ductal Breast Carcinoma

Grzegrzółka¹,

Kurnol

Piotrów

et al. 2012

Folia Histochem Cytobiol.

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Abstract:The aim of this study was to determine the intensity of Hsp27 protein expression in fibrocystic breast changes (FC) and invasive ductal breast carcinoma (IDC) and to examine its impact on patients' clinico-pathological characteristics and overall survival. Immunohistochemical reactions were conducted on archival samples of 20 cases of FC and 101 cases of IDC treated in 1999-2002. Nuclear-cytoplasmic Hsp27 expression was observed in 92 (92.1%) of the examined cases of IDC, and all the cases of FC. Significantly higher Hsp27 expression was observed in G2 (p < 0.01) and G3 cases (p < 0.0001) compared to FC. HER-2 positive cases had higher Hsp27 expression (p = 0.0153), than HER-2 negative cases. Our research showed that Hsp27 could have an impact on tumor malignancy. Moreover, a positive correlation between the expression of Hsp27 and HER-2 positive cases was demonstrated.

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Heat Shock Protein Expression in the Eye and in Uveal Melanoma

Abstract: In this study, expression of HSPs in uveal melanoma is not correlated with known histopathologic prognostic factors. The high expression of GP96 indicates that this protein is a potential vector in tumor vaccination in patients with large uveal melanomas.

Cited by 35 publications

References 37 publications

Immune Expression and Inhibition of Heat Shock Protein 90 in Uveal Melanoma

Immune Expression and Inhibition of Heat Shock Protein 90 in Uveal Melanoma

Hsps are up-regulated in melanoma tissue and correlate with patient clinical parameters

Hsp-27 Expression in Invasive Ductal Breast Carcinoma

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