scholarly journals APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis

2012 ◽  
Vol 122 (1) ◽  
pp. 419-419
Author(s):  
Qingqing Ding ◽  
Chun-Ju Chang ◽  
Xiaoming Xie ◽  
Weiya Xia ◽  
Jer-Yen Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Mouse Model ◽  
Hepatic Metastasis ◽  
Orthotopic Mouse Model

scholarly journals APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis

2011 ◽  
Vol 121 (11) ◽  
pp. 4526-4536 ◽  
Author(s):  
Qingqing Ding ◽  
Chun-Ju Chang ◽  
Xiaoming Xie ◽  
Weiya Xia ◽  
Jer-Yen Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Mouse Model ◽  
Hepatic Metastasis ◽  
Orthotopic Mouse Model

scholarly journals Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ashwani Rajput ◽  
Ekta Agarwal ◽  
Premila Leiphrakpam ◽  
Michael G. Brattain ◽  
Sanjib Chowdhury
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Mouse Model ◽  
Model System ◽  
Metastatic Tumors ◽  
Orthotopic Mouse Model ◽  
Gene Signatures ◽  
Metastatic Colonization ◽  
Disseminated Disease

Metastases are largely responsible for cancer deaths in solid tumors due to the lack of effective therapies against disseminated disease, and there is an urgent need to fill this gap. This study demonstrates an orthotopic colorectal cancer (CRC) mouse model system to develop spontaneous metastasis in vivo and compare its reproducibility against human CRC. IGF1R-dependent GEO human CRC cells were used to study metastatic colonization using orthotopic transplantation procedures and demonstrated robust liver metastasis. Cell proliferation assays were performed both in the orthotopic primary colon and liver metastatic tumors, and human CRC patient’s specimen and similar patterns in H&E and Ki67 staining were observed between the orthotopically generated primary and liver metastatic tumors and human CRC specimens. Microarray analysis was performed to generate gene signatures, compared with deposited human CRC gene expression data sets, analyzed by Oncomine, and revealed similarity in gene signatures with increased aggressive markers expression associated with CRC in orthotopically generated liver metastasis. Thus, we have developed an orthotopic mouse model that reproduces human CRC metastasis. This model system can be effective in developing new therapeutic strategies against disseminated disease and could be implemented for identifying genes that regulate the development and/or maintenance of established metastasis.

scholarly journals CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer

2020 ◽  
Author(s):  
Junwei Tang ◽  
Yifei Feng ◽  
Yuanjian Huang ◽  
Ziwei Xu ◽  
Dongsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Liver Metastasis ◽  
Hepatic Metastasis ◽  
Vascular Invasion ◽  
Synchronous Liver Metastasis ◽  
Node Negative ◽  
Common Cancer ◽  
Tumor Tissues ◽  
Colorectal Cancer Patients

Abstract Background Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer. Methods The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). The gain- and loss-of-function experiments was conducted in CRC cell lines and animal models. The RNA pull-down, RNA immunoprecipitation n was further employed in exploring the detailed mechanism of circRNA and associated target genes. Results We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly corrected with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0. Conclusions The circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.

scholarly journals Establishment of an Endoscopy-Guided Minimally Invasive Orthotopic Mouse Model of Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3007
Author(s):  
Chen Chen ◽  
Jens Neumann ◽  
Florian Kühn ◽  
Serene M. L. Lee ◽  
Moritz Drefs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Minimally Invasive ◽  
Tumor Growth ◽  
Hepatic Metastases ◽  
Specific Cell ◽  
Local Tumor ◽  
Orthotopic Mouse Model ◽  
Endoscopic Score ◽  
Local Tumor Growth

Open orthotopic mouse models of colorectal cancer have disadvantages such as the requirement for advanced surgical skills or the trauma caused by laparotomy. To overcome these drawbacks, this study aimed to evaluate the establishment of a minimally invasive model using murine colonoscopy. CT26 and MC38 CRC cells of different concentrations were injected into BALB/C and C57BL/6J mice, respectively. Follow-up endoscopies were performed to assign an endoscopic score to tumor growth. Gross autopsy, histologic and immuno-histochemical evaluation, and immune scoring were performed. To describe the learning curve of the procedures, a performance score was given. Local tumor growth with colorectal wall infiltration, luminal ulceration, the presence of tumor-infiltrating lymphocytes, lympho-vascular invasion, and early spontaneous lymph node, peritoneal, and hepatic metastases were observed. The tumors showed cytoplasmic immuno-staining for CK20. Compared to the MC38/C57BL/6J model, tumorigenicity and immunogenicity of the CT26/BALB/C model were higher. Tumor volume correlated with the endoscopic score. This endoscopy-guided orthotopic mouse model is easy to learn and quick to establish. It features early metastasis and enables the study of interactions with the immune system. When specific cell concentrations and cell lines are applied, controlled local tumor growth and metastasis can be achieved within short observation periods.

scholarly journals Establishment of a stable hepatic metastasis mouse model of murine colorectal cancer by microsurgical orthotopic implantation

2020 ◽  
Vol 9 (5) ◽  
pp. 3249-3257
Author(s):  
Zhiyun Cao ◽  
Zhideng Zhang ◽  
Liangpu Zheng ◽  
Jiumao Lin ◽  
Jun Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Hepatic Metastasis ◽  
Orthotopic Implantation

scholarly journals TCF4 enhances hepatic metastasis of colorectal cancer by regulating tumor-associated macrophage via CCL2/CCR2 signaling

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Wei Tu ◽  
Jin Gong ◽  
Zhenzhen Zhou ◽  
Dean Tian ◽  
Zhijun Wang
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Mouse Model ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Pearson Correlation ◽  
Tumor Associated Macrophage ◽  
M2 Polarization ◽  
Syngeneic Mouse Model

AbstractColorectal cancer (CRC) liver metastasis is a significant clinical problem for which better therapies are urgently needed. Tumor-associated macrophage, a major cell population in the tumor microenvironment, is a known contributor to primary cancer progression and cancer metastasis. Here, we found TAM recruitment and M2 polarization were increased in the hepatic metastatic lesion compared with the primary site of human CRC tissues. Moreover, Pearson correlation analysis showed that TAM recruitment and polarization were closely correlated with the elevated TCF4 expression in the metastatic site. To investigate the role of TCF4 in CRC liver metastasis, we generated a syngeneic mouse model using MC38 cells splenic injection. Results from in vivo experiments and mouse models revealed that TCF4 deficiency in MC38 cells does not affect their proliferation and invasion; however, it reduces TAM infiltration and M2 polarization in the metastasis site. Further studies indicated that these effects are mediated by the TCF4 regulated CCL2 and CCR2 expression. TCF4 or CCL2 silencing in the tumor cells prevent CRC liver metastasis in the mouse model. Altogether, these findings suggest that the TCF4-CCL2-CCR2 axis plays an essential role in CRC liver metastasis by enhancing TAMs recruitment and M2 polarization.

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