Reproduction of a murine model of liver metastasis of human primary malignant lymphoma of small intestine by continuous screening in vivo / 解放军医学杂志

ABSTRACT

Objective A liver metastasis model of human primary malignant lymphoma of small intestine was reproduced in nude mice in an attempt to provide an ideal animal model for elucidating the mechanism of liver metastasis of primary small intestinal lymphoma.Methods A piece of surgically obtained liver metastatic tissue of small intestinal lymphoma was implanted into the mucous membrane of small intestine in nude mice to reproduce the model.After metastasis of this tumor to the liver occurred,a portion of the metastais was transplanted into the mucous membrane of small intestine of another nude mouse.This process was repeated 4 times in order to obtain a cell line with the characteristics of high malignant lymphoma metastasis to liver.The survival rate of the experimental animals,regional invasion rate and metastasis rate were observed,and the morphological characteristics(light microscopy,electron microscopy and immunohistochemistry),karyotype analysis and DNA content of the neoplastic cells were also determined.Results A liver metastasis model of human primary malignant lymphoma of small intestine in nude mice(termed HSIL-0402)was successfully reconstructed,by repeated implantation of liver metastatic tumor in vivo.Histopathology showed HSIL-0402 tumor was a high grade non-Hodgkin's lymphoma.Immunohistology showed the cells were CD19,CD20,CD45 and CD79a positive,but negative for CD3 and CD7.The modal number of chromosome was between 56-69.DNA index(DI)was 1.61?0.37,which showed heteroploid.So far,HSIL-0402 had been maintained for 27 passages in nude mice,exhibiting 100% of transplantability,liver metastatic rate,and resuscitation rate after liquid nitrogen cryopreservation.Lymph node metastasis and celiac seeding occurred in 67.4% and 61.7% of a total of 156 observed animals.The HSIL-0402 model displayed various manifestations reminiscent of highly metastatic invasive behavior in nude mice,including invasive growth,hematogenous metastasis,lymph node metastasis and celiac seeding.Conclusion The present study successfully re-established a spontaneous liver metastasis model of human primary malignant lymphoma of small intestine in nude mice,HSIL-0402,which provides an ideal animal model for the researches on biological mechanism of liver metastasis and anti-metastasis therapy of human primary small intestinal lymphoma.