Articles by Alexander M. Betzler in JoVE
A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer Alexander M. Betzler1, Susan Kochall1, Linda Blickensdörfer2, Sebastian A. Garcia1, May-Linn Thepkaysone1, Lahiri K. Nanduri1, Michael H. Muders3, Jürgen Weitz1,4,5, Christoph Reissfelder1, Sebastian Schölch1,4,5 1Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 2Department of General, Gastrointestinal and Transplant Surgery, University of Heidelberg, 3Department of Pathology, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 4German Cancer Consortium (DKTK), 5German Cancer Research Center (DKFZ) A protocol for the establishment of a genetically engineered mouse model of colorectal cancer by segmental adeno-cre infection and its surveillance via high-resolution colonoscopy is presented.
Isolation of Circulating Tumor Cells in an Orthotopic Mouse Model of Colorectal Cancer Susan Kochall1, May-Linn Thepkaysone1, Sebastián A. García1, Alexander M. Betzler1, Jürgen Weitz1,2,3, Christoph Reissfelder1, Sebastian Schölch1,2,3 1Department of Gastrointestinal, Thoracic and Vascular Surgery, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, 2German Cancer Consortium (DKTK), 3German Cancer Research Center (DKFZ) We describe the establishment of orthotopic colorectal tumors via injection of tumor cells or organoids into the cecum of mice and the subsequent isolation of circulating tumor cells (CTCs) from this model.
Other articles by Alexander M. Betzler on PubMed
Circulating Tumor Cells Exhibit Stem Cell Characteristics in an Orthotopic Mouse Model of Colorectal Cancer Oncotarget. May, 2016 | Pubmed ID: 27029058 The prognosis of colorectal cancer (CRC) is closely linked to the occurrence of distant metastases, which putatively develop from circulating tumor cells (CTCs) shed into circulation by the tumor. As far more CTCs are shed than eventually metastases develop, only a small subfraction of CTCs harbor full tumorigenic potential. The aim of this study was to further characterize CRC-derived CTCs to eventually identify the clinically relevant subfraction of CTCs.We established an orthotopic mouse model of CRC which reliably develops metastases and CTCs. We were able to culture the resulting CTCs in vitro, and demonstrated their tumor-forming capacity when re-injected into mice. The CTCs were then subjected to qPCR expression profiling, revealing downregulation of epithelial and proliferation markers. Genes associated with cell-cell adhesion (claudin-7, CD166) were significantly downregulated, indicating a more metastatic phenotype of CTCs compared to bulk tumor cells derived from hepatic metastases. The stem cell markers DLG7 and BMI1 were significantly upregulated in CTC, indicating a stem cell-like phenotype and increased capacity of tumor formation and self-renewal. In concert with their in vitro and in vivo tumorigenicity, these findings indicate stem cell properties of mouse-derived CTCs.In conclusion, we developed an orthotopic mouse model of CRC recapitulating the process of CRC dissemination. CTCs derived from this model exhibit stem-cell like characteristics and are able to form colonies in vitro and tumors in vivo. Our results provide new insight into the biology of CRC-derived CTCs and may provide new therapeutic targets in the metastatic cascade of CRC.
LDB1 Overexpression is a Negative Prognostic Factor in Colorectal Cancer Oncotarget. Dec, 2016 | Pubmed ID: 27713177 Colorectal cancer (CRC) is the third most common cancer in western countries and is driven by the Wnt signaling pathway. LIM-domain-binding protein 1 (LDB1) interacts with the Wnt signaling pathway and has been connected to malignant diseases. We therefore aimed to evaluate the role of LDB1 in CRC.