Characterization of Stem-like Circulating Tumor Cells in Pancreatic Cancer

Zhu, Lei; Hissa, Bárbara; Győrffy, Balázs; Jann, Johann-Christoph; Yang, Cui; Reißfelder, Christoph; Schölch, Sebastian

doi:10.3390/diagnostics10050305

Cited by 11 publications

(5 citation statements)

References 89 publications

(106 reference statements)

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“…On the other hand, CTNNB1 , which encodes beta-catenin, has been linked to the EMT process, CSC pluripotency, and cancer signaling [ 67 ]. Besides, it has been seen that overexpression of CTNNB1 in CTCs has prognostic value in both cancers, melanoma [ 68 ] and pancreatic [ 69 ]. Additionally, ALDH1A1 , a stem cell marker linked with mammary stemness [ 63 ] was also increased after culture.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Ex Vivo Culture of CTCs from Advance Breast Cancer Patients: Clinical Implications

Carmona-Ule

González-Conde

Abuín

et al. 2021

Cancers

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Background: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify these surviving cells capable of forming such metastases. Methods: We isolated viable CTCs from 50 peripheral blood samples obtained from 35 patients with advanced metastatic breast cancer using RosetteSepTM for ex vivo culture. The CTCs were seeded and monitored on plates under low adherence conditions and with media supplemented with growth factors and Nanoemulsions. Phenotypic analysis was performed by immunofluorescence and gene expression analysis using RT-PCR and CTCs counting by the Cellsearch® system. Results: We found that in 75% of samples the CTC cultures lasted more than 23 days, predicting a shorter Progression-Free Survival in these patients, independently of having ≥5 CTC by Cellsearch®. We also observed that CTCs before and after culture showed a different gene expression profile. Conclusions: the cultivability of CTCs is a predictive factor. Furthermore, the subset of cells capable of growing ex vivo show stem or mesenchymal features and may represent the CTC population with metastatic potential in vivo.

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Section: Discussionmentioning

confidence: 99%

Short-Term Ex Vivo Culture of CTCs from Advance Breast Cancer Patients: Clinical Implications

Carmona-Ule

González-Conde

Abuín

et al. 2021

Cancers

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show abstract

“…On the other hand, CTNNB1, which encodes beta-catenin, has been linked to the EMT process, CSC pluripotency, and cancer signalling [67]. Besides, it has been seen that overexpression of CTNNB1 in CTCs has prognostic value in both cancers, melanoma [68] and pancreatic [69]. Additionally, ALDH1A1, a stem cell marker linked with mammary stemness [63] was also increased after culture.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Ex Vivo Culture of CTCs From Advance Breast Cancer Patients: Clinical Implications

Carmona-Ule

González-Conde

Abuín

et al. 2021

Preprint

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Background: Circulating tumor cells (CTC) have relevance as prognostic markers in breast cancer. However, the functional properties of CTCs or their molecular characterization have not been well-studied. Experimental models indicate that only a few cells can survive in the circulation and eventually metastasize. Thus, it is essential to identify these surviving cells capable of forming such metastases. Methods: We isolated viable CTCs from 50 peripheral blood samples obtained from 35 patients with advanced metastatic breast cancer using RosetteSepTM for ex vivo culture. The CTCs were seeded and monitored on plates under low adherence conditions and with media supplemented with growth factors and Nanoemulsions. Phenotypic analysis was performed by immunofluorescence and gene expression analysis using RT-PCR and CTCs counting by Cellsearch® system. Results: We found that in 75% of samples the CTC cultures lasted more than 23 days, predicting a shorter Progression-Free Survival in these patients, independently of having ≥ 5 CTC by Cellsearch®. We also observed that CTCs before and after culture showed a different gene expression profile. Conclusions: the cultivability of CTCs is a predictive factor. Furthermore, the subset of cells capable of growing ex vivo show stem or mesenchymal features and may represent the CTC population with metastatic potential in vivo.

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“…The current literature recognizes the critical role of epithelial cell adhesion molecule (EPCAM) in identifying CTCs due to its absence in normal blood cells [ 49 , 50 ]. However, there is increasing concern that CTCs may at least partially lose epithelial traits, including EPCAM expression during epithelial–mesenchymal transition (EMT) [ 51 , 52 , 53 , 54 , 55 ]. For instance, only 40% (30/75) of the murine pancreatic CTCs in GSE51372 express EPCAM.…”

Section: Discussionmentioning

confidence: 99%

GAS2L1 Is a Potential Biomarker of Circulating Tumor Cells in Pancreatic Cancer

Zhu

Kan

Grün

et al. 2020

Cancers

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Pancreatic cancer is a malignant disease with high mortality and a dismal prognosis. Circulating tumor cell (CTC) detection and characterization have emerged as essential techniques for early detection, prognostication, and liquid biopsy in many solid malignancies. Unfortunately, due to the low EPCAM expression in pancreatic cancer CTCs, no specific marker is available to identify and isolate this rare cell population. This study analyzed single-cell RNA sequencing profiles of pancreatic CTCs from a genetically engineered mouse model (GEMM) and pancreatic cancer patients. Through dimensionality reduction analysis, murine pancreatic CTCs were grouped into three clusters with different biological functions. CLIC4 and GAS2L1 were shown to be overexpressed in pancreatic CTCs in comparison with peripheral blood mononuclear cells (PBMCs). Further analyses of PBMCs and RNA-sequencing datasets of enriched pancreatic CTCs were used to validate the overexpression of GAS2L1 in pancreatic CTCs. A combinatorial approach using both GAS2L1 and EPCAM expression leads to an increased detection rate of CTCs in PDAC in both GEMM and patient samples. GAS2L1 is thus proposed as a novel biomarker of pancreatic cancer CTCs.

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Characterization of Stem-like Circulating Tumor Cells in Pancreatic Cancer

Cited by 11 publications

References 89 publications

Short-Term Ex Vivo Culture of CTCs from Advance Breast Cancer Patients: Clinical Implications

Short-Term Ex Vivo Culture of CTCs from Advance Breast Cancer Patients: Clinical Implications

Short-Term Ex Vivo Culture of CTCs From Advance Breast Cancer Patients: Clinical Implications

GAS2L1 Is a Potential Biomarker of Circulating Tumor Cells in Pancreatic Cancer

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