Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers

Zhao, Yue; Li, Jiahui; Li, Dai; Wang, Zhefang; Zhao, Jiangang; Wu, Xiaolin; Sun, Qiye; Lin, Peter Ping; Plum, Patrick Sven; Damanakis, Alexander; Gebauer, Florian; Zhou, Menglong; Zhang, Zhen; Schlößer, Hans; Jauch, Karl Walter; Nelson, Peter J.; Bruns, Christiane

doi:10.1016/j.semcancer.2019.08.026

Cited by 35 publications

(32 citation statements)

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“…CSCs, therefore, are the central nodes of transdifferentiation. Among the transdifferentiated TECs in carcinoma patients, some express TMs as either shown in this review or demonstrated previously by us [ 11 , 12 , 13 ].…”

Section: Mechanism Of Tumor-derived Ec and Ctec Formation: Endothesupporting

confidence: 78%

“…Compared to transdifferentiation, cell fusion principally accounts for the observed cell identity changes [ 75 ]. Among individual non-hematologic CTECs [ 12 , 13 ] and their clusters [ 11 , 12 ] obtained from either transdifferentiation or cell fusion, those harboring a mixed phenotype of both endothelial lineage and various tumor markers (TMs) are either aneuploid or infrequently diploid.…”

Section: Mechanism Of Tumor-derived Ec and Ctec Formation: Endothementioning

confidence: 99%

“…Despite the existence of null CTECs in carcinoma patients, some CD31 + /CD45 – CTECs expressing various TMs, such as HER2, PD-L1, and EpCAM, were detected by the integrated strategy of “subtraction enrichment-immunostaining-fluorescence in situ hybridization (SE-iFISH)” (Cytelligen, USA) [ 11 , 14 , 76 ] in varieties of cancer patients [ 11 , 12 , 13 ]. Additional TM + mononuclear aneuploid CTECs, DTECs, and their multinuclear heterokaryon clusters in cancer patients are revealed in Figure 2 .…”

Section: Mechanism Of Tumor-derived Ec and Ctec Formation: Endothementioning

confidence: 99%

“…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%

“…Following their shedding into peripheral blood, TECs turn into circulating tumor-derived endothelial cells (CTECs) [ 11 ]. Some CTECs in different types of carcinoma patients were found to express a variety of tumor and mesenchymal markers, such as HER2, PD-L1, EpCAM, CD44v6 and Vimentin [ 11 , 12 , 13 ]. Aneuploid CD31 + CTECs and their counterpart CD31 – CTCs compose a unique pair of cellular circulating tumor biomarkers in cancer patients [ 12 , 14 ].…”

Section: Introductionmentioning

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: Mechanism Of Tumor-derived Ec and Ctec Formation: Endothesupporting

confidence: 78%

Section: Mechanism Of Tumor-derived Ec and Ctec Formation: Endothementioning

confidence: 99%

Section: Mechanism Of Tumor-derived Ec and Ctec Formation: Endothementioning

confidence: 99%

Section: Hypoxia Induces Cancer Metastasis and Tumor Neovascularizmentioning

confidence: 99%

Section: Introductionmentioning

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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Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma

et al. 2022

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ImportanceThe optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear.ObjectivesTo evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC.Design, Setting, and ParticipantsThis prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021.ExposuresAll patients received chemotherapy alone or CCRT.Main Outcomes and MeasuresThe primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation.ResultsAmong the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P &lt; .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P &lt; .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P &lt; .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P &lt; .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P &lt; .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification.Conclusions and RelevanceIn this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.

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Role of aneuploid circulating tumor cells and CD31⁺ circulating tumor endothelial cells in predicting and monitoring anti‐angiogenic therapy efficacy in advanced NSCLC

Zhang

Gao

et al. 2021

Molecular Oncology

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Prognosticating the efficacy of anti‐angiogenic therapy through longitudinal monitoring and early detection of treatment resistance in cancer patients remain highly challenging. In this study, co‐detection and comprehensive phenotypic and karyotypic molecular characterization of aneuploid circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) were conducted on non‐small cell lung cancer (NSCLC) patients receiving bevacizumab plus chemotherapy. Prognostic values of the cell‐based significant univariate risk factors identified by Cox regression analyses were progressively investigated. Subjects showing an increase in total post‐therapeutic platelet endothelial cell adhesion molecule‐1 (CD31)– CTCs and CD31+ CTECs exhibited a significantly reduced median progression‐free survival (mPFS) and overall survival. Further stratification analyses indicated that pretherapeutic patients bearing vimentin (Vim)+ CTECs (mesenchymal M‐type) at baseline revealed a significantly shortened mPFS compared with patients with Vim– CTECs. Post‐therapeutic patients harboring epithelial cell adhesion molecule (EpCAM)+ CTCs and CTECs (epithelial E‐type), regardless of Vim expression or not, showed a significantly reduced mPFS. Post‐therapeutic patients possessing de novo EpCAM+/Vim+ (hybrid E/M‐type) CTECs displayed the shortest mPFS. Patients harboring either pre‐ or post‐therapeutic EpCAM–/Vim– null CTECs (N‐type) exhibited a better response to therapy compared to patients harboring EpCAM+ and/or Vim+ CTECs. The presented results support the notion that baseline Vim+ CTECs and post‐therapeutic EpCAM+ CTCs and CTECs are predictive biomarkers for longitudinal monitoring of response to anti‐angiogenesis combination regimens in NSCLC patients.

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Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers

Cited by 35 publications

References 154 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

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma

Role of aneuploid circulating tumor cells and CD31⁺ circulating tumor endothelial cells in predicting and monitoring anti‐angiogenic therapy efficacy in advanced NSCLC

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Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers

Cited by 35 publications

References 154 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

Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma

Role of aneuploid circulating tumor cells and CD31+ circulating tumor endothelial cells in predicting and monitoring anti‐angiogenic therapy efficacy in advanced NSCLC

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Product

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Role of aneuploid circulating tumor cells and CD31⁺ circulating tumor endothelial cells in predicting and monitoring anti‐angiogenic therapy efficacy in advanced NSCLC