Abstract
BackgroundA mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis. In this paper, we established a mouse model of metastatic human gastric cancer in nude mice that has a higher rate of tumor formation and metastasis than existing models.MethodsTo generate the mouse model of metastatic human gastric cancer, fresh tumor tissues from patients that have undergone surgery for gastric cancer were subcutaneously implanted in the right and left groins of nude mice. When the implanted tissue grew to 1 cubic centimeter, the mice were killed, and the tumor tissues were examined and resected. The tumor tissues were implanted into nude mice and subjected to pathological examination, immunohistochemical staining, and real-time PCR for cytokeratin 8/18 (CK8/18), E-cadherin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The mice were also analyzed for metastasis in their peritoneum, abdominal cavity, and internal organs by histopathological examination. Tissues collected from these organs were examined for pathology.ResultsAfter ten generations of implantation, all mice developed tumor growth at the implanted position, 94 % of the mice developed metastasis to the retroperitoneum and viscera. The implanted and metastatic tumor maintained the same histological features across all generations, and metastasis was observed in the esophagus, stomach, spleen, liver, kidney, adrenal, intestine, and pancreas. These metastatic tumors revealed no detectable expression of CK8/18, E-cadherin, VCAM-1, and ICAM-1.ConclusionsThis model will serve as valuable tool for understanding the metastatic process of human gastric cancer.
Highlights
A mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis
Many mouse models of metastatic human gastric cancer have been generated by orthotopic transplantation of gastric cancer tissue [15,16,17,18]
We described a mouse model of metastatic human stomach cancer that addresses the issues from previous mouse models
Summary
A mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis. We established a mouse model of metastatic human gastric cancer in nude mice that has a higher rate of tumor formation and metastasis than existing models. A metastatic model of human colon cancer was first constructed by Morikawa in 1988 using human colon cancer cells subserously implanted into cecum [11] This model showed orthotopic tumor growth and liver metastasis. Furukawa further modified this model in 1993 by surgically stitching human gastric cancer tissue into the tunica serosa gastria of nude mice [12]. This model developed tumors robustly and showed a very high rate of metastasis to the liver. Many mouse models of metastatic human gastric cancer have been generated by orthotopic transplantation of gastric cancer tissue [15,16,17,18]
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