Expression and prognostic value of putative cancer stem cell markers CD117 and CD15 in choroidal and ciliary body melanoma

Lukenda, Adrian; Dotlić, Snježana; Vukojević, Nenad; Šarić, Borna; Vranić, Semir; Žarković, Kamelija

doi:10.1136/jclinpath-2015-203130

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…Several studies explored the KIT expression and its prognostic significance in UM [ 21 , 22 , 38 , 39 , 40 ]. KIT positivity, detected in 20 of 48 (41.7%) samples analyzed in our study, agrees to 54% positivity reported by Lukenda et al, using the identical >10% cutoff [ 21 ]. However, with a 50% cutoff, Lüke et al found high KIT expression in 63% of UM patients [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cyclin D1 (Cyclin-D1-binding protein 1), Ki-67 (Proliferation marker protein Ki-67), and p53 (Cellular tumor antigen p53) positivities were linked with an unfavorable outcome [ 20 ]. Likewise, the overexpression of transmembrane tyrosine kinase receptor KIT (Mast/stem cell growth factor receptor Kit, alternative name CD117) was associated with poor prognosis in choroidal and ciliary body UM [ 21 , 22 ]. We recently identified 5-fold upregulation of its mRNA in M3 tumors compared to those with two copies of chromosome 3 (disomy 3, D3) [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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KIT Expression Is Regulated by DNA Methylation in Uveal Melanoma Tumors

Kajabova

Šoltýsová

Demkova

et al. 2021

IJMS

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Uveal melanoma (UM) is an ocular tumor with a dismal prognosis. Despite the availability of precise molecular and cytogenetic techniques, clinicopathologic features with limited accuracy are widely used to predict metastatic potential. In 51 UM tissues, we assessed a correlation between the expression of nine proteins evaluated by immunohistochemistry (IHC) (Melan-A, S100, HMB45, Cyclin D1, Ki-67, p53, KIT, BCL2, and AIFM1) and the presence of UM-specific chromosomal rearrangements measured by multiplex ligation-dependent probe amplification (MLPA), to find IHC markers with increased prognostic information. Furthermore, mRNA expression and DNA methylation values were extracted from the whole-genome data, achieved by analyzing 22 fresh frozen UM tissues. KIT positivity was associated with monosomy 3, increasing the risk of poor prognosis more than 17-fold (95% CI 1.53–198.69, p = 0.021). A strong negative correlation was identified between mRNA expression and DNA methylation values for 12 of 20 analyzed positions, five located in regulatory regions of the KIT gene (r = −0.658, p = 0.001; r = −0.662, p = 0.001; r = −0.816; p < 0.001; r = −0.689, p = 0.001; r = −0.809, p < 0.001, respectively). DNA methylation β values were also inversely associated with KIT protein expression (p = 0.001; p = 0.001; p = 0.015; p = 0.025; p = 0.002). Our findings, showing epigenetic deregulation of KIT expression, may contribute to understanding the past failure to therapeutically target KIT in UM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

KIT Expression Is Regulated by DNA Methylation in Uveal Melanoma Tumors

Kajabova

Šoltýsová

Demkova

et al. 2021

IJMS

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“…Given that stem cells have the ability of self-renewal, unlimited proliferation, drug resistance, high invasion and express high levels of CD117 and CD133 (18,19), we identified highly invasive populations of A2780 and A2780-PTX cells through Transwell assays. We screened the drug-resistant ovarian cancer cell line A2780-PTX for a highly drug-resistant ovarian cancer cell population with high invasiveness, and designated this population A2780-PTX-PM.…”

Section: Discussionmentioning

confidence: 99%

Effects and mechanism of RhoC downregulation in suppressing ovarian cancer stem cell proliferation, drug resistance, invasion and metastasis

et al. 2016

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Cancer stem cells are considered to be the root cause of tumor initiation, metastasis, recurrence and therapeutic resistance. Recent studies have reported that RhoC plays a critical role in regulating cancer stem cells; however, its function in ovarian cancer stem cells (OCSCs) remains unknown. The ovarian cancer cell line A2780, and the paclitaxel-resistant A2780 cell line (A2780-PTX) were obtained. A2780 cells were used to isolate and identify the highly invasive A2780-PM cells, and A2780-PTX cells were used to isolate and identify the highly drug-resistant and highly invasive A2780-PTX-PM cells by Transwell assay. MTT, Transwell and wound healing assays were used to compare the differences in cell proliferation, invasion and migration ability among the four cell lines. Immunofluorescence was used to detect the expression of stem cell markers CD117 and CD133. OCSCs were sorted by flow cytometry. Following si-RhoC transfection of the OCSCs, cell proliferation, drug resistance, invasion and migration ability and RhoC, CD117 and CD133 expression levels were assayed. RT-PCR was used to assess RhoC, CD117, CD133 and matrix metalloproteinase 9 (MMP9) mRNA expression levels. A2780-PM and A2780‑PTX-PM cells exhibited higher cell proliferation, drug resistance, and invasion and migration ability than the A2780 and A2780-PTX cell lines. Furthermore, CD133 and CD117 expression levels were higher in the A2780-PM and A2780‑PTX-PM cells than levels in the A2780 and A2780-PTX cells. Transfection of si-RhoC in OCSCs suppressed the proliferation, drug resistance, invasion, migration and CD117 and CD133 expression levels. Furthermore, the expression levels of RhoC, CD117, CD133, MDR1, and MMP9 mRNA were downregulated in the transfected population. Taken together, our results demonstrated that RhoC downregulation may inhibit the proliferation, drug resistance, invasion and migration of OCSCs, and RhoC may play an important role in the formation of OCSCs.

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“…In addition, choroidal and ciliary body melanoma CSCs express CD117 and CD15 markers [88]. Overall, these studies suggest that tumors of various organs consist of distinct CSC populations with different stemness phenotypes.…”

Section: Manifold Existence Of Cancer Stem Cells and Its Impact On Camentioning

confidence: 99%

“…CD44 + and CD133 + cells have been proposed to be CSCs of medullary thyroid carcinoma [85], endometrial cancers [86] and rectal cancer [87]. In addition, choroidal and ciliary body melanoma CSCs express CD117 and CD15 markers [88]. Overall, these studies suggest that tumors of various organs consist of distinct CSC populations with different stemness phenotypes.…”

Section: Manifold Existence Of Cancer Stem Cells and Its Impact On Camentioning

confidence: 99%

Unraveling the journey of cancer stem cells from origin to metastasis

Nimmakayala

Batra

Ponnusamy

2019

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Cancer biology research over recent decades has given ample evidence for the existence of self-renewing and drug-resistant populations within heterogeneous tumors, widely recognized as cancer stem cells (CSCs). However, a lack of clear understanding about the origin, existence, maintenance, and metastatic roles of CSCs limit efforts towards the development of CSC-targeted therapy. In this review, we describe novel avenues of current CSC biology. In addition to cell fusion and horizontal gene transfer, CSCs are originated by mutations in somatic or differentiated cancer cells, resulting in de-differentiation and reprogramming. Recent studies also provided evidence for the existence of distinct or heterogeneous CSC populations within a single heterogeneous tumor. Our analysis of the literature also opens the doors for a novel hypothesis that CSC populations with specific phenotypes, metabolic profiles, and clonogenic potential metastasize to specific organs.

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Expression and prognostic value of putative cancer stem cell markers CD117 and CD15 in choroidal and ciliary body melanoma

Abstract: 3

Cited by 10 publications

References 23 publications

KIT Expression Is Regulated by DNA Methylation in Uveal Melanoma Tumors

KIT Expression Is Regulated by DNA Methylation in Uveal Melanoma Tumors

Effects and mechanism of RhoC downregulation in suppressing ovarian cancer stem cell proliferation, drug resistance, invasion and metastasis

Unraveling the journey of cancer stem cells from origin to metastasis

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