Tumor cell markers in uveal melanoma

Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.

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Expression of CD133 and other putative stem cell markers in uveal melanoma

Melanoma Research ◽

10.1097/cmr.0b013e328348db10 ◽

2011 ◽

Vol 21 (5) ◽

pp. 405-416 ◽

Cited By ~ 19

Author(s):

Michelle Thill ◽

Marc Jean Berna ◽

Rebecca Grierson ◽

Inna Reinhart ◽

Tobias Voelkel ◽

...

Keyword(s):

Stem Cell ◽

Uveal Melanoma ◽

Stem Cell Markers ◽

Cell Markers ◽

Putative Stem Cell

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Analysis of Circulating Tumour Cells in Early-Stage Uveal Melanoma: Evaluation of Tumour Marker Expression to Increase Capture

Cancers ◽

10.3390/cancers13235990 ◽

2021 ◽

Vol 13 (23) ◽

pp. 5990

Author(s):

Aaron B. Beasley ◽

Timothy W. Isaacs ◽

Tersia Vermeulen ◽

James Freeman ◽

Jean-Louis DeSousa ◽

...

Keyword(s):

Stem Cell ◽

Cell Lines ◽

Uveal Melanoma ◽

Early Stage ◽

Tumour Cells ◽

Stem Cell Markers ◽

Circulating Tumour Cells ◽

Marker Panel ◽

Cell Markers ◽

Molecular Features

(1) Background: The stratification of uveal melanoma (UM) patients into prognostic groups is critical for patient management and for directing patients towards clinical trials. Current classification is based on clinicopathological and molecular features of the tumour. Analysis of circulating tumour cells (CTCs) has been proposed as a tool to avoid invasive biopsy of the primary tumour. However, the clinical utility of such liquid biopsy depends on the detection rate of CTCs. (2) Methods: The expression of melanoma, melanocyte, and stem cell markers was tested in a primary tissue microarray (TMA) and UM cell lines. Markers found to be highly expressed in primary UM were used to either immunomagnetically isolate or immunostain UM CTCs prior to treatment of the primary lesion. (3) Results: TMA and cell lines had heterogeneous expression of common melanoma, melanocyte, and stem cell markers. A multi-marker panel of immunomagnetic beads enabled isolation of CTCs in 37/43 (86%) patients with UM. Detection of three or more CTCs using the multi-marker panel, but not MCSP alone, was a significant predictor of shorter progression free (p = 0.040) and overall (p = 0.022) survival. (4) Conclusions: The multi-marker immunomagnetic isolation protocol enabled the detection of CTCs in most primary UM patients. Overall, our results suggest that a multi-marker approach could be a powerful tool for CTC separation for non-invasive prognostication of UM.

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PD-1 expression on uveal melanoma induces tumor proliferation and predicts poor patient survival

The International Journal of Biological Markers ◽

10.1177/1724600820943610 ◽

2020 ◽

Vol 35 (3) ◽

pp. 50-58

Author(s):

Zhongming Jiang ◽

Yuexiang Yan ◽

Juan Dong ◽

Lingling Duan

Keyword(s):

Cell Proliferation ◽

Tumor Cell ◽

Cell Lines ◽

Uveal Melanoma ◽

Patient Survival ◽

Malignant Tumors ◽

Tumor Diameter ◽

Tumor Cell Proliferation ◽

Poor Patient ◽

Poor Patient Survival

Introduction: Uveal melanoma is one of the most common primary intraocular malignant tumors with poor prognosis and limited treatments. Programmed cell death receptor-1 (PD-1) blockade represents the primary treatment strategy of immune checkpoint inhibition; however, there is a lack of studies on whether PD-1 expression in primary (ocular) uveal melanoma affects tumor progression. Methods: PD-1 expression in 82 cases of primary (ocular) uveal melanoma was detected by immunohistochemistry. The clinical significance of PD-1 expression was evaluated using univariate and multivariate analysis. PD-1 overexpression and knockdown studies were conducted in C918 and Mum-2B cell lines to analyze the effect of PD-1 expression on tumor cell proliferation and intracellular cell signaling transduction. real-time qPCR (RT-qPCR) and western blot analysis were performed to investigate the gene expression level. CCK8 assays were performed to examine the cell proliferation ability. Results: High expression of primary (ocular) intratumor PD-1 was associated with poor patient survival. Moreover, PD-1 expression was correlated with the largest tumor diameter. PD-1 expression and optic nerve invasion were independent prognostic risk factors. PD-1 overexpression in uveal melanoma cell lines promoted tumor cell proliferation, while knockdown of PD-1 inhibited cell proliferation capacity. Conclusion: Our study established the role of PD-1 in the progression of uveal melanoma and provided a new potential treatment selection for uveal melanoma.

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Abstract 4953: Single cell signaling analysis reveals circulating tumor cell markers of drug susceptibility and tumor heterogeneity

10.1158/1538-7445.am2017-4953 ◽

2017 ◽

Author(s):

N Murat Karabacak ◽

Yu Zheng ◽

Erin Emmons ◽

Michael Koulopoulos ◽

Daniel A. Haber ◽

...

Keyword(s):

Tumor Cell ◽

Cell Signaling ◽

Single Cell ◽

Tumor Heterogeneity ◽

Circulating Tumor Cell ◽

Drug Susceptibility ◽

Cell Markers

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HL-325: A Case Report of Classic Hodgkin Lymphoma with Unusually Abundant Tumor Cell Expression of B-Cell Markers: A Diagnostic Dilemma and Treatment Challenge

Clinical Lymphoma Myeloma & Leukemia ◽

10.1016/s2152-2650(21)01852-8 ◽

2021 ◽

Vol 21 ◽

pp. S372-S373

Author(s):

Irina Panovska-Stavridis ◽

Nevenka Ridova ◽

Simona Stojanovska ◽

Aleksandra Pivkova-Veljanovska ◽

Sanja Trajkova ◽

...

Keyword(s):

Case Report ◽

Tumor Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Diagnostic Dilemma ◽

Cell Markers ◽

Classic Hodgkin Lymphoma ◽

Cell Expression

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Correlations Between Visual Acuity, Presenting Symptoms and Histopathological Findings in Enucleated Eyes with Uveal Melanoma

10.21203/rs.3.rs-952903/v1 ◽

2021 ◽

Author(s):

Elin Asplund ◽

Tony Pansell ◽

Rune Brautaset ◽

Maria Nilsson ◽

Gustav Stålhammar

Keyword(s):

Visual Acuity ◽

Tumor Cell ◽

Uveal Melanoma ◽

Histopathological Examination ◽

Vasculogenic Mimicry ◽

Tumor Thickness ◽

Cell Type ◽

Basal Diameter ◽

Presenting Symptoms ◽

Blurry Vision

Abstract Visual outcomes after treatment of uveal melanoma have been investigated repeatedly. In this paper, we evaluate the correlation between visual acuity (VA) prior to enucleation, presenting symptoms and findings upon histopathological examination of eyes and tumors. Sixty nine patients were included. Their mean best corrected visual acuity (BCVA) prior to enucleation was LogMAR 0.80 (SD 0.70). Patients that reported low VA or blurry vision did not have lower BCVA upon refraction (p=0.34). Patients with low BCVA had tumors with greater apical tumor thickness (p=0.027), basal diameter (p=0.012) and stage (p=0.014). The experience of a shadow in the visual field correlated with presence of vasculogenic mimicry in the tumor (p<0.001). In multivariate Cox regressions with tumor thickness and diameter as covariates, tumor cell type and infiltration of the optic nerve head were associated with increased hazard for melanoma-related mortality (3.2 and 3.6, respectively). We conclude that patients that report low VA do not necessarily have worse BCVA. The latter do however have tumors with larger dimensions, at more advanced stage. A shadow in the VF correlates with presence of vasculogenic mimicry, which is an independent predictor for poor prognosis along with tumor infiltration of the optic disc and tumor cell type.

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