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 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.

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 LncRNA MIR17HG promotes colorectal cancer liver metastasis by mediating a glycolysis-associated positive feedback circuit

Oncogene ◽  
2021 ◽  
Author(s):  
Senlin Zhao ◽  
Bingjie Guan ◽  
Yushuai Mi ◽  
Debing Shi ◽  
Ping Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Metastatic Tumor ◽  
Feedback Circuit ◽  
Colorectal Cancer Liver Metastasis ◽  
Positive Feedback Circuit

AbstractGlycolysis plays a crucial role in reprogramming the metastatic tumor microenvironment. A series of lncRNAs have been identified to function as oncogenic molecules by regulating glycolysis. However, the roles of glycolysis-related lncRNAs in regulating colorectal cancer liver metastasis (CRLM) remain poorly understood. In the present study, the expression of the glycolysis-related lncRNA MIR17HG gradually increased from adjacent normal to CRC to the paired liver metastatic tissues, and high MIR17HG expression predicted poor survival, especially in patients with liver metastasis. Functionally, MIR17HG promoted glycolysis in CRC cells and enhanced their invasion and liver metastasis in vitro and in vivo. Mechanistically, MIR17HG functioned as a ceRNA to regulate HK1 expression by sponging miR-138-5p, resulting in glycolysis in CRC cells and leading to their invasion and liver metastasis. More interestingly, lactate accumulated via glycolysis activated the p38/Elk-1 signaling pathway to promote the transcriptional expression of MIR17HG in CRC cells, forming a positive feedback loop, which eventually resulted in persistent glycolysis and the invasion and liver metastasis of CRC cells. In conclusion, the present study indicates that the lactate-responsive lncRNA MIR17HG, acting as a ceRNA, promotes CRLM through a glycolysis-mediated positive feedback circuit and might be a novel biomarker and therapeutic target for CRLM.

scholarly journals Characterization of Lung Cancer by Amide Proton Transfer (APT) Imaging: An In-Vivo Study in an Orthotopic Mouse Model

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e77019 ◽  
Author(s):  
Osamu Togao ◽  
Chase W. Kessinger ◽  
Gang Huang ◽  
Todd C. Soesbe ◽  
Koji Sagiyama ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Proton Transfer ◽  
In Vivo Study ◽  
Amide Proton ◽  
Orthotopic Mouse Model ◽  
Amide Proton Transfer ◽  
Apt Imaging

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.

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