Dynamic monitoring of CD45-/CD31+/DAPI+ circulating endothelial cells aneuploid for chromosome 8 during neoadjuvant chemotherapy in locally advanced breast cancer

Ma, Ge; Jiang, Yi; Liang, Mengdi; Wang, Jenny; Mao, Xiao‐Ming; Veeramootoo, Jordee Selvamanee; Xia, Tiansong; Li, Xiaoan; Wang, Shui

doi:10.1177/1758835920918470

Cited by 17 publications

(17 citation statements)

References 38 publications

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“…Dynamic changes in the epithelial and mesenchymal composition of CTCs were recently reported [ 99 , 100 ]. EpCAM + and Vimentin + aneuploid CTCs and CTECs, produced by the transdifferentiation of CSCs or heterotypic cell fusion of cancer cells with ECs, were detected in cancer patients with a variety of epithelial carcinomas [ 11 , 12 , 13 , 101 ]. EpCAM + neoplastic cells showed diminished sensitivity toward growth factor deprivation and increased tumorigenicity [ 44 ].…”

Section: Hypoxia Induces Cancer Metastasis and Tumor Neovascularizmentioning

confidence: 99%

“…Furthermore, postsurgical small EpCAM + multiploid rare cells in circulation were found to correlate with HCC patients’ postoperative recurrence [ 83 ]. Recently, following the positive detection of multiploid EpCAM + CTECs in locally advanced breast cancer patients receiving neoadjuvant chemotherapy [ 101 ], multiploid and triploid PD-L1 + CTECs were reported to respectively show intrinsic and acquired resistance to the immunotherapeutic agent nivolumab (Opdivo) in NSCLC patients [ 12 ].…”

Section: Clinical Significance and The Novel Therapeutic Target Pomentioning

confidence: 99%

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Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis

Lin

2020

Cells

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Hematogenous and lymphogenous cancer metastases are significantly impacted by tumor neovascularization, which predominantly consists of blood vessel-relevant angiogenesis, vasculogenesis, vasculogenic mimicry, and lymphatic vessel-related lymphangiogenesis. Among the endothelial cells that make up the lining of tumor vasculature, a majority of them are tumor-derived endothelial cells (TECs), exhibiting cytogenetic abnormalities of aneuploid chromosomes. Aneuploid TECs are generated from “cancerization of stromal endothelial cells” and “endothelialization of carcinoma cells” in the hypoxic tumor microenvironment. Both processes crucially engage the hypoxia-triggered epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT). Compared to the cancerization process, endothelialization of cancer cells, which comprises the fusion of tumor cells with endothelial cells and transdifferentiation of cancer cells into TECs, is the dominant pathway. Tumor-derived endothelial cells, possessing the dual properties of cancerous malignancy and endothelial vascularization ability, are thus the endothelialized cancer cells. Circulating tumor-derived endothelial cells (CTECs) are TECs shed into the peripheral circulation. Aneuploid CD31+ CTECs, together with their counterpart CD31- circulating tumor cells (CTCs), constitute a unique pair of cellular circulating tumor biomarkers. This review discusses a proposed cascaded framework that focuses on the origins of TECs and CTECs in the hypoxic tumor microenvironment and their clinical implications for tumorigenesis, neovascularization, disease progression, and cancer metastasis. Aneuploid CTECs, harboring hybridized properties of malignancy, vascularization and motility, may serve as a unique target for developing a novel metastasis blockade cancer therapy.

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Section: Hypoxia Induces Cancer Metastasis and Tumor Neovascularizmentioning

confidence: 99%

Section: Clinical Significance and The Novel Therapeutic Target Pomentioning

confidence: 99%

Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis

Lin

2020

Cells

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“…CTCs, CECs, and CACs are well-known for their association with metastasis and progression and provide information for individual therapy and prediction of prognosis in several cancer types such as breast, colorectal, prostate, and lung ( 7 , 12 – 17 ). Epithelial markers such as EpCAM and cytokeratin are often used to enrich CTCs ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

Small Cell Size Circulating Aneuploid Cells as a Biomarker of Prognosis in Resectable Non-Small Cell Lung Cancer

Yang

Zhang

et al. 2021

Front. Oncol.

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ObjectiveThe size distribution of circulating aneuploid cells (CACs) and its clinical significance were investigated in resectable non-small cell lung cancer (NSCLC).Patients and MethodsA total of 50 patients with resectable NSCLC were enrolled in this study. Blood samples (50 pre-surgery and 35 post-surgery) were collected and used for the detection of CAC chromosome 8 heteroploidy through the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method.ResultsLess than 20% small cell size and more than 80% large cell size CACs were detected. Karyotypes, including triploid, tetraploid, and multiploid, had varying distributions. The triploid subtype accounted for the majority of small cell size CACs, whereas the multiploid subtype accounted for the majority of large cell size CACs. We found that total small cell size and triploid small cell size CACs, but not large cell size CACs, derived from pre-surgery samples, were associated with shorter disease-free survival. Moreover, total small cell size and triploid small cell size CACs were associated with higher TNM stage and recurrence. Nevertheless, the variation between pre- and post-surgery CACs was not related to survival among patients with resectable NSCLC.ConclusionsPre-surgery small cell size CACs, especially the triploid subtype, could be regarded as a potential prognostic biomarker for patients with resectable NSCLC.

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“… 28 The levels of aneuploid CTEC may be influenced by neoadjuvant chemotherapy in patients with locally advanced breast cancer. 29 CTECs expressing stemness marker of CD44 in PDAC patients remain to be investigated. 10 Poruk KE et al proved that CTCs labeled with stemness marker such as CD44 are independent predictors of decreased disease-free and overall survival.…”

Section: Discussionmentioning

confidence: 99%

CD44+ Circulating Tumor Endothelial Cells Indicate Poor Prognosis in Pancreatic Ductal Adenocarcinoma After Radical Surgery: A Pilot Study

Cheng

Ding

et al. 2021

CMAR

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Background Circulating tumor endothelial cells (CTECs) are cells that originate from tumor endothelial cells (TECs) of blood vessels and are shed into peripheral blood. Some studies have shown that CTECs are associated with tumor angiogenesis, growth and indicate prognosis in patients with malignant solid tumor. However, the role of CTECs especially the phenotype of CTECs in pancreatic adenocarcinoma (PDAC) is still not clear. We investigated the relationship between CTECs and patients’ prognosis. Methods A total of 73 patients with resectable PDAC were enrolled in our research and underwent radical surgery. Peripheral venous blood samples were collected before surgery, on postoperative day (POD) 7 and on postoperative month (POM) 1, respectively. We used integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) platform to identify and enumerate CTECs. Immunofluorescence was used to identify CTECs expressing CD44 and vimentin. Results In patients with early tumor recurrence (DFS< 6 months), the preoperative CD44+ CTEC levels showed significantly higher ( P = 0.023). Univariate and multivariate analysis showed that history of diabetes [HR 2.656 (1.194–5.908), P = 0.017], numbers of positive lymph nodes [HR 1.871 (1.388–2.522), P < 0.001], preoperative numbers of CD44+ CTECs [HR 1.216 (1.064–1.390), P = 0.004], and POM1 CA19-9 level [HR 1.002 (1.001–1.002), P < 0.001] were independent prognostic factors for DFS. Conclusion The detection of CD44+CTECs in patients with resectable PDAC preoperatively could be an independent predictor of shorter DFS after radical surgery.

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Dynamic monitoring of CD45-/CD31+/DAPI+ circulating endothelial cells aneuploid for chromosome 8 during neoadjuvant chemotherapy in locally advanced breast cancer

Cited by 17 publications

References 38 publications

Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis

Aneuploid Circulating Tumor-Derived Endothelial Cell (CTEC): A Novel Versatile Player in Tumor Neovascularization and Cancer Metastasis

Small Cell Size Circulating Aneuploid Cells as a Biomarker of Prognosis in Resectable Non-Small Cell Lung Cancer

CD44+ Circulating Tumor Endothelial Cells Indicate Poor Prognosis in Pancreatic Ductal Adenocarcinoma After Radical Surgery: A Pilot Study

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