Neuroblastoma Cells Circulate in Peripheral Blood

Lanino, E.; Melodia, A.; Casalaro, Antonella; Cornaglia-Ferraris, P.

doi:10.3109/08880018909034286

Cited by 6 publications

(6 citation statements)

References 3 publications

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“…Using CCT2 as a marker for CTCs adds pertinent information on the potential for the detected CTCs to originate from an aggressive or invasive cancer. Previous studies to detect CTCs from neuroblastoma patients used immunological methods with antibodies targeting neuron markers like GD2, CD56, or CD90 (65)(66)(67)(68). However, such methods, while specific, in the absence of an enrichment step, have low sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma

et al. 2022

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Chaperonin containing TCP1 (CCT/TRiC) is a multi-subunit protein folding complex that enables the cancer phenotype to emerge from the mutational landscape that drives oncogenesis. We and others linked increased expression of CCT subunits to advanced tumor stage and invasiveness that inversely correlates with cancer patient outcomes. In this study, we examined the expression of the second CCT subunit, CCT2, using genomic databases of adult and pediatric tumors and normal tissues, and found that it was highly expressed in pediatric cancers, showing a significant difference compared to normal tissues. Histologic staining confirmed that CCT subunits are highly expressed in tumor tissues, which was exemplified in neuroblastoma. Using two neuroblastoma cells, MYCN-amplified, IMR-32 cells, and non-amplified, SK-N-AS cells, we assessed baseline levels for CCT subunits and found expressions comparable to the highly invasive triple-negative breast cancer (TNBC) cell line, MDA-MB-231. Exogenous expression of CCT2 in both SK-N-AS and IMR-32 cells resulted in morphological changes, such as larger cell size and increased adherence, with significant increases in the CCT substrates, actin, and tubulin, as well as increased migration. Depletion of CCT2 reversed these effects and reduced cell viability. We evaluated CCT as a therapeutic target in IMR-32 cells by testing a novel peptide CCT inhibitor, CT20p. Treatment with CT20p induced cell death in these neuroblastoma cells. The use of CCT2 as a biological indicator for detection of neuroblastoma cells shed in blood was examined by spiking IMR-32 cells into human blood and using an anti-CCT2 antibody for the identification of spiked cancer cells with the CellSearch system. Results showed that using CCT2 for the detection of neuroblastoma cells in blood was more effective than the conventional approach of using epithelial markers like cytokeratins. CCT2 plays an essential role in promoting the invasive capacity of neuroblastoma cells and Frontiers in Oncology frontiersin.org 01

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Section: Discussionmentioning

confidence: 99%

Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma

et al. 2022

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“…Immunocytochemical methods have been applied to detect NB CTCs using monoclonal antibodies targeting NB‐specific neuron markers including GD2, CD56 and CD90 (THY1). 41 , 42 , 43 ICC allows for the identification of around 1–2 CTCs among 10 5 peripheral blood mononuclear cells (PBMCs) 44 without previous enrichment. Though the reliability of CTC detection and qualification in NB by ICC methods has remained inconclusive, it is recommended by INRG to use GD2 for the detection of rare NB tumor cells in BM, PB and PBSC through ICC.…”

Section: Enrichment and Detection Methods For Ctcs In Nbmentioning

confidence: 99%

Circulating tumor cells in neuroblastoma: Current status and future perspectives

2022

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Neuroblastoma is the most common extracranial solid tumor in children, accounting for 10% to 20% of deaths of pediatric malignancies. Due to the poor prognosis and significant biological heterogeneity of neuroblastoma, it is essential to develop personalized therapeutics and monitor treatment response. Circulating tumor cells (CTCs), as one of the important analytes for liquid biopsy, could facilitate response assessment and outcome prediction for patients in a non‐invasive way. Several methods and platforms have been used for the enrichment and detection of CTCs. The enumeration of CTCs counts and evaluation of tumor‐specific mRNA transcript levels could provide prognostic information at diagnosis, during or after chemotherapy, and during the process of disease progression. So far, studies into neuroblastoma CTCs are only in the preliminary stages. The quality‐controlled large prospective cohort studies are needed to evaluate the clinical significance and statistical rigor of CTC detection methods. Moreover, there remains a lot to be explored and investigated in genotyping characterization of neuroblastoma (NB) CTCs and construction of in‐vitro or in‐vivo functional models. CTCs and circulating tumor DNA (ctDNA) analysis will be complementary in understanding tumor heterogeneity and evolution over the course of therapy for patients with NB in the future.

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“…The first prospective molecular analyses of CTCs employed immunocytochemical methods with monoclonal antibodies against neuronal cell markers such as CD56 (NCAM), CD90 (Thy-1) and GD2 [168,170,171]. CTCs were detected in patients with metastatic disease at diagnosis [168,170,171], during therapy [170,171] and at relapse [168]. In one study, the presence of CTCs in patients with metastatic disease during therapy was found to be an indicator of disease relapse [170].…”

Section: Ctc Detection Methodsmentioning

confidence: 99%

“…CTCs are currently under investigation as biomarkers for diagnosis, therapeutic monitoring, prognostication and assessment of relapse risk [166]. The presence of CTCs in patients with NB was first demonstrated through the establishment of NB cell lines during in vitro culture of peripheral blood samples from patients with disseminated disease [167,168]. These studies highlighted the potential for tumour cell contamination in stem cell harvests from peripheral blood, a concern supported by a later study demonstrating the clonogenic properties of NB CTCs in vitro [169].…”

Section: Emerging Tumour-specific Circulating Biomarkers In Neuroblasmentioning

confidence: 99%

“…CTC, circulating tumour cell; EFS, event-free survival; FISH, fluorescence in situ hybridization; ICC, immunocytochemistry; MRD, minimal residual disease; NB, neuroblastoma; ND, not determined; RT-(q)PCR, reverse transcription (quantitative real-time) PCR; INSS, International Neuroblastoma Staging System; OS, overall survival; PFS, progression-free survival.detection method(s)marker(s)sensitivity (tumour cell n /non-tumour cell n )main observation(s) in peripheral bloodstudyICCNCAM, unknown NB-specific antigenNDCTCs detected in patients with metastatic disease at diagnosis and relapse.Lanino et al . [168]ICCGD2, Thy-1, unknown NB-specific antigen2/10 5 CTCs detected in patients with metastatic disease at diagnosis and during therapy.The presence of CTCs in patients during therapy associated with disease relapse.Moss & Sanders [170]ICCGD2, Thy-1, unknown NB-specific antigenNDCTCs detected in patients with metastatic disease at diagnosis. CTCs detected during therapy in one patient.Sanders et al .…”

Section: Emerging Tumour-specific Circulating Biomarkers In Neuroblasmentioning

confidence: 99%

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Opportunities and challenges of circulating biomarkers in neuroblastoma

2019

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Molecular analysis of nucleic acid and protein biomarkers is becoming increasingly common in paediatric oncology for diagnosis, risk stratification and molecularly targeted therapeutics. However, many current and emerging biomarkers are based on analysis of tumour tissue, which is obtained through invasive surgical procedures and in some cases may not be accessible. Over the past decade, there has been growing interest in the utility of circulating biomarkers such as cell-free nucleic acids, circulating tumour cells and extracellular vesicles as a so-called liquid biopsy of cancer. Here, we review the potential of emerging circulating biomarkers in the management of neuroblastoma and highlight challenges to their implementation in the clinic.

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Neuroblastoma Cells Circulate in Peripheral Blood

Cited by 6 publications

References 3 publications

Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma

Chaperonin containing TCP-1 (CCT/TRiC) is a novel therapeutic and diagnostic target for neuroblastoma

Circulating tumor cells in neuroblastoma: Current status and future perspectives

Opportunities and challenges of circulating biomarkers in neuroblastoma

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