Circulating Tumor Cell Clusters: United We Stand Divided We Fall

Amintas, Samuel; Bedel, Aurélie; Moreau‐Gaudry, François; Boutin, Julian; Buscail, Louis; Merlio, Jean-Philippe; Vendrely, V.; Dabernat, Sandrine; Buscail, Étienne

doi:10.3390/ijms21072653

Cited by 77 publications

(48 citation statements)

References 65 publications

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“…Also, overestimation of keratins positive cells was avoided, since CD45 was used as an exclusion marker for PBMCs. We individually analyzed single CTCs and clusters, since accumulating data support distinct biological features and clinical relevance between these two CTC populations [ 4 , 6 , 7 , 46 ]. CTC clusters were detected in almost 40% of CTC-positive patients, and in accordance with previous reports in MBC and NSCLC, we observed that the EMT phenotype was more frequent among cluster than in among single CTCs [ 4 , 6 , 8 ].…”

Section: Discussionmentioning

confidence: 99%

“…CTCs are found either as single cells or in clusters, while their phenotypic analysis has shown significant intra- and inter-patient heterogeneity [ 4 ]. The detection of CTCs in clusters and their contribution in metastasis and poor outcome of patients has been highlighted in various cancers [ 5 , 6 , 7 , 8 ]. The molecular characteristics and properties of clusters are different from those of single CTCs [ 6 , 7 ] and their size considerably varies, from 2 to 100 CTCs [ 4 , 6 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Polioudaki

Mala

Gkimprixi

et al. 2020

Cancers

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We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients’ outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1+mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1+mCTCs and especially single PD-L1+mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1+mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1+mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Polioudaki

Mala

Gkimprixi

et al. 2020

Cancers

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“…In addition, CTC clusters can initiate the formation of polyclonal metastases [ 25 , 26 , 51 , 53 ], suggesting the existence of a mechanism of cooperation between cancer cell clones within CTC clusters that can have relevant implications in the disease evolution, and in particular in the diagnosis and treatment of the metastatic disease. For a deeper insight about the biology of CTC clusters, the most recent knowledge is summarized in references [ 24 , 46 , 54 ].…”

Section: Circulating Tumor Cells (Ctcs)mentioning

confidence: 99%

Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs)

Hurtado¹,

Martínez-Pena²,

Piñeiro

2020

Cancers

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The crosstalk between cancer cells and the tumor microenvironment (TME) is a key determinant of cancer metastasis. Cancer-associated fibroblasts (CAFs), one of the main cellular components of TME, promote cancer cell invasion and dissemination through mechanisms including cell-cell interactions and the paracrine secretion of growth factors, cytokines and chemokines. During metastasis, circulating tumor cells (CTCs) are shed from the primary tumor to the bloodstream, where they can be detected as single cells or clusters. The current knowledge about the biology of CTC clusters positions them as key actors in metastasis formation. It also indicates that CTCs do not act alone and that they may be aided by stromal and immune cells, which seem to shape their metastatic potential. Among these cells, CAFs are found associated with CTCs in heterotypic CTC clusters, and their presence seems to increase their metastatic efficiency. In this review, we summarize the current knowledge on the role that CAFs play on metastasis and we discuss their implication on the biogenesis, metastasis-initiating capacity of CTC clusters, and clinical implications. Moreover, we speculate about possible therapeutic strategies aimed to limit the metastatic potential of CTC clusters involving the targeting of CAFs as well as their difficulties and limitations.

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“…A minority of CTCs could also be present as clusters of CTCs that have stable cell-cell junctions [ 108 ]. These latters are associated with worse clinical outcome when compared to a single CTC [ 107 , 109 ]. Moreover, recent in vivo evidence showed that CTC clusters presented a stronger invasive potential over single CTCs [ 110 ].…”

Section: Circulating Biomarkers To Predict Response To Ncrt In Larmentioning

confidence: 99%

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

Palma

Luglio

Tropeano

et al. 2020

IJMS

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The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

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Circulating Tumor Cell Clusters: United We Stand Divided We Fall

Cited by 77 publications

References 65 publications

Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs)

The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

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