Comparison of Different Colorectal Cancer With Liver Metastases Models Using Six Colorectal Cancer Cell Lines
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ORIGINAL ARTICLE
Comparison of Different Colorectal Cancer With Liver Metastases Models Using Six Colorectal Cancer Cell Lines Yuting Xu 1 & Lin Zhang 1 & Qingling Wang 1 & Maojin Zheng 1 Received: 19 May 2019 / Accepted: 4 March 2020 # Arányi Lajos Foundation 2020
Abstract At present, modeling methods of colorectal cancer with liver metastases have significant limitations. Here, we established orthotopic and ectopic hepatic metastases models using six colorectal cancer cell lines to choose an ideal animal model for studying colorectal cancer growth and liver metastases. Luciferin-expressing six colorectal cancer cell lines were used to induce animal models of colorectal cancer with liver metastases by intra-splenic injection or implantation of tumor tissue in the caecum. Tumors growth and metastatic events were observed by bioluminescence imaging. In orthotopic transplantation group, six cell lines all had taken rates of 100% for orthotopic tumors but showed variations in rates of growth. HCT-116 cell developed the 50% liver metastases. However, the ectopic transplantation group achieved higher liver metastatic rate, with the highest frequencies for HCT116 cell (90%) and SW620 cell (77.8%). Furthermore, the time to develop liver metastases and survival rates of bearingtumor mice were shorter than orthotopic transplantation group. Additionally, six colorectal cancer cell lines resulted in more lymph node metastases in orthotopic transplantation group, whereas produced widespread peritoneal seeding in ectopic transplantation group. Bioluminescence imaging and pathological findings confirmed the growth and metastatic characteristics of tumors. Two animal models of colorectal cancer using six cell lines showed highly variations in rates of growth, survival rates of bearing-tumor mice and frequencies of metastases. The study provides useful information for the establishment of clinically relevant colorectal cancer with liver metastases animal models. Keywords Colorectal cancer cell lines . Liver metastases . Orthotopic model . Ectopic model
Introduction Colorectal cancer (CRC) is the third most commonly diagnosed cancer in males and the second in females, it is estimated that there will be 1.4 million cases and 693,900 deaths attributable to this disease in 2012 [1, 2]. Despite presenting with a resectable primary tumor, 20–25% patients progress to distant metastases, mainly to liver, 5-year survival rate of patients diagnosed with distant metastases decreases to less than 10% [3, 4]. Therefore, there is an urgent need for new treatment strategies to improve the prognosis of CRC patients with liver metastases. Animals models are essential to the mechanistic research and development of effective therapeutics. At
* Yuting Xu [email protected] 1
Department of Pathology, Xuzhou Medical University, 221004 Xuzhou, Jiangsu, China
present, metastatic disease can be modeled using orthotopic implantation and ectopic implantation. The former includes injection of CRC cells or implantation of tumor tissue in the colon, cec
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