A murine model of human primary hepatic lymphoma constructed by surgical orthotopic implantation of histologically intact human tumor tissue and in vivo continuous orthotopic passage

Abstract

To establish a nude murine model of human primary hepatic lymphoma (PHL) with surgical orthotopic implantation of histologically intact human tumor tissue and in vivo continuous orthotopic passage. Histologically intact lymphoma tissues harvested intraoperatively from a PHL patient were orthotopically transplanted into liver parenchyma of nude mice and in vivo continuous orthotopic passage in nude mice was used to develop a nude murine model mimicking the biological characteristics of PHL patients. Histopathology (light microscopy and immunohistochemistry), serological test, karyotypic analysis and flow cytometry were used to explore the tumorigenicity, invasion and metastasis. An orthotopic nude murine model of PHL, named HLBL-0102, was successfully developed. Histopathology of transplanted tumors showed primary hepatic lymphoma (diffuse large B cell) stained positive for CD20, CD79a and MUM1. Serological test in tumor-bearing mice indicated that alpha-fetal protein (AFP) was negative and hepatitis B surface antigen (HBsAg) positive. The serum level of lactate dehydrogenase (LDH) was elevated to an average of ((1223 ± 258) vs (124 ± 54) U/L, P < 0.01). The chromosomal number of transplanted tumors was between 55 and 59. The DNA index (DI) of 1.7 ± 0.2 indicated heteroploid. So far HLBL-0102 model has been passed for 42 generations in nude mice. A total of 320 nude mice were used for transplantation. The growth rate and resuscitation rate of liquid nitrogen cryopreservation of transplanted tumors were both 100%. The transplanted tumors grew invasively in the liver of nude mice and destroyed adjacent liver tissues and bile ducts, veins and arteries of portal area. There was no involvement of other tissues, organs and distal lymph nodes. An orthotopically transplanted model has been successfully established for human primary hepatic lymphoma in nude mice.