Nestin and vimentin colocalization affects the subcellular location of glucocorticoid receptor in cutaneous melanoma

Lai, Simone; Piras, Franca; Spiga, Saturnino; Perra, Maria Teresa; Minerba, Luigi; Piga, M; Mura, Ester; Murtas, Daniela; Demurtas, Paolo; Corrias, Michela; Maxia, Cristina; Ferreli, Caterina; Sirigu, P.

doi:10.1111/his.12018

Cited by 9 publications

(13 citation statements)

References 48 publications

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“…Previous studies reported that nestin is a prognostic factor in cutaneous melanoma [13,[19][20][21]. Our study also showed the same results; nestin was significantly associated with disease progression in multivariate analyses.…”

Section: Discussionsupporting

confidence: 90%

“…These results suggest that nestin expression activates migrating melanocytes, not just malignant cells. A recent study reported that nestin is involved in the invasion mechanism of melanoma [19,21]. Therefore, immunodetection of nestin cannot be used to distinguish a benign lesion from a malignant lesion, but may be useful for prognosis prediction in advanced-stage melanoma [10].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of nestin in primary malignant melanoma of the oral cavity

Kuk

Won²,

Lee³

et al. 2016

Melanoma Research

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Several studies have examined the correlation between nestin expression and the degree of tumor invasion in cutaneous melanoma. However, no information has been reported on nestin in primary mucosal melanoma of the head and neck. The present study examined the expression and prognostic significance of nestin in patients with primary mucosal melanoma of the oral cavity. Nestin expression was examined immunohistochemically in 39 patients (six oral melanoma in-situ cases and 33 invasive oral melanoma cases) and analyzed for association with disease progression. Age, sex, anatomic site, stage, level of invasion, regional lymph node metastasis, surgical margin involvement, and treatment modality were also analyzed. In the 33 invasive melanoma cases, invasion depth correlated significantly with prognosis in univariate and multivariate analyses. High-intensity nestin staining was observed in 14 of the 33 cases and a high proportion of nestin-positive cells was observed in 16 cases. In stage III oral melanoma cases, nestin expression was not significantly associated with disease progression. However, in stage IV cases, both the intensity and the proportion of nestin expression were significantly associated with disease progression (P=0.022 and 0.005, respectively). In all 33 invasive cases, multivariate analyses showed that both the intensity and the proportion of nestin were significantly associated with a poor prognosis (P=0.014 and 0.009; hazard ratio, 3.59 and 4.05; 95% confidence interval, 1.29-9.98 and 1.42-11.56, respectively). In conclusion, nestin can be a valuable prognostic indicator in the advanced-stage (stage IV) cases of oral mucosal melanoma.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Prognostic significance of nestin in primary malignant melanoma of the oral cavity

Kuk

Won²,

Lee³

et al. 2016

Melanoma Research

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“…GCs are important stress hormones and are used as a concomitant medication during malignant tumor chemotherapy. Current studies have suggested a positive relationship between GCs and melanoma progression (27,(36)(37)(38). The mechanism by which GC influences melanoma biology is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that GCs have no significant direct effects on the proliferation of most human melanoma cells in vitro, but giving liposomal prednisolone phosphate (PLP) for prolonged periods of time reduces the melanoma growth by inhibiting tumor angiogenesis in mice (25,26). Recently a clinicopathological study demonstrated that the subcellular distribution of GR in cutaneous melanoma specimens is associated with tumor thickness and Clark level, the level of anatomical invasion of melanoma in the skin (27). However, it is still unclear whether GCs affect the adhesion and survival of melanoma cells.…”

Section: Introductionmentioning

confidence: 99%

Involvement of upregulation of fibronectin in the pro‑adhesive and pro‑survival effects of glucocorticoid on melanoma cells

Huang

et al. 2017

Mol Med Report

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Glucocorticoids (GCs) are important stress hormones, which are used as a concomitant medication during malignant tumor chemotherapy. Clinical and preclinical studies have linked GCs to melanoma growth and progression. However, the effects and mechanism of action of GCs on the adhesion and survival of melanoma cells are still unknown. In the present study the effect of dexamethasone (Dex), a synthetic GC, on fibronectin (FN) expression and its roles in regulating the adhesion and survival of melanoma cells were investigated. It was revealed that Dex significantly increased the levels of intracellular and secreted FN in melanoma cell lines by increasing glucocorticoid receptor‑mediated FN protein stability. Additionally, it was demonstrated that Dex (100 nM) significantly promoted the adhesion and survival of melanoma cells. Silencing FN expression abrogated the pro‑adhesive and pro‑survival effects of Dex in melanoma cells. Extracellular FN significantly enhanced melanoma cell adhesion and survival in the presence of cisplatin, whereas partially blocking extracellular FN signaling with a CD44 antibody significantly reduced FN‑enhanced adhesion and survival. This indicated that the upregulation of FN contributed to the pro‑survival effect of Dex by enhancing cell adhesion. It was also observed that activation of the PI3K/AKT signaling pathway by extracellular FN was involved in the FN‑mediated increase in melanoma cell survival. These findings increase understanding of the possible mechanisms by which GCs regulate melanoma cell adhesion and survival.

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“…The intermediate filament protein nestin is a neuroectodermal stem/progenitor cell marker [ 8 – 9 ]. Self-renewing melanoma progenitor cells expressed nestin [ 10 ] and both intermediate filament proteins nestin and vimentin were found to colocalize in melanoma [ 11 ]. Next to neural cells and melanocytes, the neural crest also generates mesenchymal cell types and nestin was detected in mesodermal cells like fibroblasts or hepatic stellate cells [ 12 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

et al. 2015

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BackgroundThe epithelioid and sarcomatoid histologic variants of malignant pleural mesothelioma (MPM) can be considered as E- and M-parts of the epithelial-mesenchymal transition (EMT) axis; the biphasic being an intermediate. EMT is associated with an increase of stem cell (SC) traits. We correlated the neural crest SC marker nestin and the EMT marker periostin with histology, type of neo-adjuvant chemotherapy (CT) and overall survival (OS) of MPM patients.Patients and MethodsTumor tissues of a historic cohort 1 (320 patients) and an intended induction chemotherapy followed by extrapleural pneumonectomy (EPP) cohort 2 (145 patients) were immunohistochemically H-scored (intensity of immunoreactivity multiplied by frequency of stained cells). Paired chemo-naïve biopsies and -treated surgical specimens were available for 105/145 patients. CT included platinum/gemcitabine (Pla/Gem) or platinum/pemetrexed (Pla/Pem).ResultsExpression of any cytosolic nestin progressively increased from epithelioid to biphasic to sarcomatoid MPM in cohort 1, whereas the diagnostic markers calretinin and podoplanin decreased. In cohort 2, Pla/Pem CT increased the expression level of nestin in comparison to Pla/Gem, whereas the opposite was found for periostin. In Pla/Pem treated patients, nestin was higher in biphasic MPM compared to epithelioid. In addition to non-epithelioid histology, any expression of nestin in chemo-naïve biopsies (median overall survival: 22 vs. 17 months) and chemo-treated surgical specimens (18 vs. 12 months) as well as high periostin in biopsies (23 vs. 15 months) were associated with poor prognosis. In the multivariate survival analysis, any nestin expression in chemo-naïve biopsies proved to be an independent prognosticator against histology. In both pre- and post-CT situations, the combination of nestin or periostin expression with non-epithelioid histology was particularly/ dismal (all p-values <0.05).ConclusionsThe SC marker nestin and the EMT marker periostin allow for further prognostic stratification among histologic variants of MPM. Their expression level is influenced by neo-adjuvant chemotherapy.

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Nestin and vimentin colocalization affects the subcellular location of glucocorticoid receptor in cutaneous melanoma

Abstract: These results suggest the presence in melanoma of growth mechanisms involving nestin, vimentin, and GR, similarly to that occurring in embryonic and undifferentiated cells, and may help in understanding tumour biology to provide a molecular basis for clinical therapies.

Cited by 9 publications

References 48 publications

Prognostic significance of nestin in primary malignant melanoma of the oral cavity

Prognostic significance of nestin in primary malignant melanoma of the oral cavity

Involvement of upregulation of fibronectin in the pro‑adhesive and pro‑survival effects of glucocorticoid on melanoma cells

Expression of the Stem Cell Factor Nestin in Malignant Pleural Mesothelioma Is Associated with Poor Prognosis

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