Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma

Anand, Kartik; Roszik, Jason; Gombos, Dan S.; Upshaw, Joshua R.; Sarli, Vanessa N.; Meas, Salyna; Lucci, Anthony; Hall, Carolyn; Patel, Sapna

doi:10.3390/cancers11060856

Cited by 32 publications

(43 citation statements)

References 18 publications

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“…Metastasis is rarely found during diagnosis of primary UM and many patients already have organ specific micrometastases by the time the ocular tumor is detected [ 98 ]. Moreover, CTCs have been detected at primary UM diagnosis, preceding the clinical detection of metastasis [ 99 ]. There remains an urgent need for tools that will aid in the screening and monitoring of tumor burden.…”

Section: Discussionmentioning

confidence: 99%

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Tsering

Laskaris

Abdouh

et al. 2020

Cancers

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Extracellular vesicles (EVs) carry molecules derived from donor cells and are able to alter the properties of recipient cells. They are important players during the genesis and progression of tumors. Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is associated with a high rate of metastasis, primarily to the liver. However, the mechanisms underlying this process are poorly understood. In the present study, we analyzed the oncogenic potential of UM-derived EVs and their protein signature. We isolated and characterized EVs from five UM cell lines and from normal choroidal melanocytes (NCMs). BRCA1-deficient fibroblasts (Fibro-BKO) were exposed to the EVs and analyzed for their growth in vitro and their reprograming potential in vivo following inoculation into NOD-SCID mice. Mass spectrometry of proteins from UM-EVs and NCM-EVs was performed to determine a protein signature that could elucidate potential key players in UM progression. In-depth analyses showed the presence of exosomal markers, and proteins involved in cell-cell and focal adhesion, endocytosis, and PI3K-Akt signaling pathway. Notably, we observed high expression levels of HSP90, HSP70 and integrin V in UM-EVs. Our data bring new evidence on the involvement of UM-EVs in cancer progression and metastasis.

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Section: Discussionmentioning

confidence: 99%

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Tsering

Laskaris

Abdouh

et al. 2020

Cancers

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“…Gorges et al 2019CellSearch R Melanoma Kit CTC positivity in early-stage disease correlated with OS at 24 months. Anand et al (2019) Strong correlation between CTC positivity and PFS and OS; and between CTC numbers and ctDNA-levels. Bidard et al (2014) Prospective study of stage IV patients.…”

Section: Proteoglycans In Circulating Tumor Cell Diagnosticsmentioning

confidence: 99%

The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis

Ahrens

Bang-Christensen

Jørgensen³

et al. 2020

Front. Cell Dev. Biol.

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Circulating tumor cells (CTCs) are accessible by liquid biopsies via an easy blood draw. They represent not only the primary tumor site, but also potential metastatic lesions, and could thus be an attractive supplement for cancer diagnostics. However, the analysis of rare CTCs in billions of normal blood cells is still technically challenging and novel specific CTC markers are needed. The formation of metastasis is a complex process supported by numerous molecular alterations, and thus novel CTC markers might be found by focusing on this process. One example of this is specific changes in the cancer cell glycocalyx, which is a network on the cell surface composed of carbohydrate structures. Proteoglycans are important glycocalyx components and consist of a protein core and covalently attached long glycosaminoglycan chains. A few CTC assays have already utilized proteoglycans for both enrichment and analysis of CTCs. Nonetheless, the biological function of proteoglycans on clinical CTCs has not been studied in detail so far. Therefore, the present review describes proteoglycan functions during the metastatic cascade to highlight their importance to CTCs. We also outline current approaches for CTC assays based on targeting proteoglycans by their protein cores or their glycosaminoglycan chains. Lastly, we briefly discuss important technical aspects, which should be considered for studying proteoglycans.

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“…CTCs were collected from blood samples (from 7.5 mL to 50 mL) in combination with anticoagulant agents (heparin or EDTA). CTCs process was performed up to 72 h following the collection [29,35]. Immunomagnetic and sizing methods mainly collect CTCs with Cellsearch, which is the only FDA approved CTC collector device [29,31,32,35].…”

Section: Ctc Isolation and Identificationmentioning

confidence: 99%

Liquid Biopsy for Solid Ophthalmic Malignancies: An Updated Review and Perspectives

Martel

Baillif²,

Nahon-Estève³

et al. 2020

Cancers

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Tissue biopsy is considered the gold standard when establishing a diagnosis of cancer. However, tissue biopsies of intraocular ophthalmic malignancies are hard to collect and are thought to be associated with a non-negligible risk of extraocular dissemination. Recently, the liquid biopsy (LB) has emerged as a viable, non-invasive, repeatable, and promising way of obtaining a diagnosis, prognosis, and theragnosis of patients with solid tumors. LB refers to blood, as well as any human liquid. The natural history of uveal melanoma (UM) and retinoblastoma (RB) are radically opposed. On the one hand, UM is known to disseminate through the bloodstream, and is, therefore, more accessible to systemic venous liquid biopsy. On the other hand, RB rarely disseminates hematogenous, and is, therefore, more accessible to local liquid biopsy by performing an anterior chamber puncture. In this review, we summarize the current knowledge concerning LB in UM, RB, conjunctival tumors, and choroidal metastases. We also develop the current limitations encountered, as well as the perspectives.

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Pilot Study of Circulating Tumor Cells in Early-Stage and Metastatic Uveal Melanoma

Cited by 32 publications

References 18 publications

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

Uveal Melanoma-Derived Extracellular Vesicles Display Transforming Potential and Carry Protein Cargo Involved in Metastatic Niche Preparation

The Role of Proteoglycans in Cancer Metastasis and Circulating Tumor Cell Analysis

Liquid Biopsy for Solid Ophthalmic Malignancies: An Updated Review and Perspectives

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