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Liebl contributed equally to this work and are co–first authors. in: JCI | Pub Med | Google Scholar European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, United Kingdom. Phone: 49.912; E-mail: [email protected] note: A. This approach was based on the hypothesis that isolated TECs in culture may stably maintain TME-induced changes in their transcriptomes due to TME-dependent imprinting processes. Address correspondence to: Michael Stürzl, Division of Molecular and Experimental Surgery, University Medical Center Erlangen and Friedrich-Alexander-University of Erlangen-Nuremberg, Translational Research Center, Schwabachanlage 12, D-91054 Erlangen, Germany. The aim of this study was to investigate the impact on TEC plasticity and heterogeneity of 2 TMEs that are associated with different prognoses of patients with CRC. Liebl contributed equally to this work and are co–first authors. in: JCI | Pub Med | Google Scholar European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, United Kingdom. Phone: 49.912; E-mail: [email protected] note: A. However, few studies have yet investigated the phenotypic and genotypic variability of stromal cells associated with different TMEs. Address correspondence to: Michael Stürzl, Division of Molecular and Experimental Surgery, University Medical Center Erlangen and Friedrich-Alexander-University of Erlangen-Nuremberg, Translational Research Center, Schwabachanlage 12, D-91054 Erlangen, Germany. The heterogeneity of tumor cells may also induce the plasticity and, as a consequence, the heterogeneity of the stromal cells. Liebl contributed equally to this work and are co–first authors. in: JCI | Pub Med | Google Scholar European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, United Kingdom. Here, we isolated pure TECs from human colorectal carcinomas (CRCs) that exhibited TMEs with either improved (Th1-TME CRCs) or worse clinical prognosis (control-TME CRCs). The impact of TME-dependent heterogeneity of tumor endothelial cells (TECs) on tumorigenesis is unclear.

Address correspondence to: Michael Stürzl, Division of Molecular and Experimental Surgery, University Medical Center Erlangen and Friedrich-Alexander-University of Erlangen-Nuremberg, Translational Research Center, Schwabachanlage 12, D-91054 Erlangen, Germany. It was also highly expressed in ECs in healthy colon tissues and Th1-TME CRCs but low in control-TME CRCs.

Liebl contributed equally to this work and are co–first authors. in: JCI | Pub Med | Google Scholar European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, United Kingdom. Phone: 49.912; E-mail: [email protected] note: A. Accordingly, EC heterogeneity was detected in tumors arising from different organs ().

Address correspondence to: Michael Stürzl, Division of Molecular and Experimental Surgery, University Medical Center Erlangen and Friedrich-Alexander-University of Erlangen-Nuremberg, Translational Research Center, Schwabachanlage 12, D-91054 Erlangen, Germany. Endothelial cells (ECs) originating from different vascular beds are heterogeneous with respect to gene expression and cellular structure.

Liebl contributed equally to this work and are co–first authors. in: JCI | Pub Med | Google Scholar European Cancer Stem Cell Research Institute, Cardiff University, Cardiff, United Kingdom. Phone: 49.912; E-mail: [email protected] note: A. The TME can activate or restrain tumor progression, malignancy, or the occurrence of metastasis ().

Address correspondence to: Michael Stürzl, Division of Molecular and Experimental Surgery, University Medical Center Erlangen and Friedrich-Alexander-University of Erlangen-Nuremberg, Translational Research Center, Schwabachanlage 12, D-91054 Erlangen, Germany. This mutual crosstalk is commonly referred to as the tumor microenvironment (TME).

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