Fascin expression in melanocytic lesions of the skin

Yıldız, Levent; Kefeli, Mehmet; Aydın, Oğuz; Kandemır, Bedrı

doi:10.1684/ejd.2009.0716

Cited by 11 publications

(8 citation statements)

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“…[29][30][31][32] Melanomas have been found to express the stem-cell markers nestin, CD166, CD133, ATP-binding cassette subfamily B member 5 and CD20, 29,33,34 leading to characterization of subpopulations of 'melanoma stem cells', and the proposal that melanoma could arise from dermal stem cells rather than mature melanocytes. 31,35 Furthermore, altered expression of certain stem-cell markers in melanoma, such as increased nestin, 36,37 decreased fascin 38,39 and CD133 positivity, 30 have been associated with increased malignant potential and metastasis.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem‐cell phenotype

et al. 2013

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Background Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations; however, the lineage of the mutated cells remains uncertain.Objectives To test the hypothesis that CMN may be derived from cutaneous stem cells.Methods Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (nestin, fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67) and MTOR/Wnt-signalling pathway activation (pS6, β-catenin). Semiquantitative scoring compared samples with naevus cell nesting (group 1) with those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples.Results A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and was stronger superficially. Expression of β-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli.Conclusions Congenital melanocytic naevi development frequently coexists with normal overlying melanocyte development, leading us to hypothesize that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem-cell origin, capable of some degree of melanocytic differentiation superficially.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem‐cell phenotype

et al. 2013

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“…The two proteins with abundance differences meeting the significance criteria were the exogenously expressed E-cadherin (human) and fascin. Fascin is a globular actin crosslinking protein (F-actin), which is commonly observed to exhibit differential expression in melanomas, but has not been shown to affect disease progression or outcomes (32,33). Fascin has been observed to be upregulated in B16F10 melanoma versus the less metastatic variant, B16F0 (34).…”

Section: Exogenous Expression Of E-cadherin In B16f10 Exerts Minimal mentioning

confidence: 99%

Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma

et al. 2019

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Identifying controlling features of responsiveness to checkpoint blockade therapies is an urgent goal in oncology research. Our group and others have previously shown melanoma tumors resistant to checkpoint blockade display features of mesenchymal transition, including E-cadherin loss. Here, we present the first in vivo evidence that E-cadherin from tumor cells facilitate immune attack, using a B16F10 melanoma mouse model in which E-cadherin is exogenously expressed (B16.Ecad). We find, compared with vector control, B16.Ecad exhibits delayed tumor growth, reduced metastatic potential, and increased overall survival in vivo. Transplantation of B16.Ecad into Rag1 À/À and CD103 À/À mice abrogated the tumor growth delay. This indicates the antimelanoma response against B16.Ecad is both immune and CD103 þ mediated. Moreover, B16.Ecad showed increased responsiveness to combination immune checkpoint blockade (ICB) compared with vector control. This work establishes a rationale for ICB responses observed in high E-cadherin-expressing tumors and suggests therapeutic advancement through amplifying CD103 þ immune cell subsets. Significance: These findings identify the mechanism behind checkpoint blockade resistance observed in melanoma that has undergone mesenchymal transition and suggest activation of CD103 þ immune cells as a therapeutic strategy against other E-cadherin-expressing malignancies.

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“…Fascin‐1 is present in normal melanocytes 93, and clinical studies report an inverse relationship between fascin‐1 expression and malignant or metastatic melanomas 93–95. This would indicate that melanoma invasion/metastasis relies on factors other than fascin‐1.…”

Section: Roles Of Fascins In Diseasementioning

confidence: 99%

The roles of fascins in health and disease

Hashimoto

Kim

Adams

2011

The Journal of Pathology

173

202

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Fascins are actin-binding proteins that cross-link filamentous actin into tightly packed parallel bundles. These bundles are important for the organization and morphology of an extremely diverse set of sub-cellular structures that include dynamic and stable cell-surface protrusions, stress fibres, and the specialized actin bundles of photoreceptor and stereocilia cells. In this review, we discuss the fascin gene family and its evolution, the actin-bundling activity of fascins and the molecular pathways by which it is regulated, and the role of the diverse actin/fascin structures in normal cellular processes. We discuss the mechanisms by which fascins contribute to disease pathologies, especially cancer, where fascin-1 is emerging as a novel therapeutic target in carcinoma metastasis.

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Fascin expression in melanocytic lesions of the skin

Cited by 11 publications

References 0 publications

Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem‐cell phenotype

Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem‐cell phenotype

Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint Blockade Responsiveness in Melanoma

The roles of fascins in health and disease

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