Establishment of high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation / 解放军医学杂志

ABSTRACT

Objective To reproduce high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation, and to investigate their biologic features. Methods Histologically fresh lymphoma tissues from primary and liver metastatic lesions of human primary colorectal lymphoma obtained during operations were transplanted into colorectal mucosa of nude mice. Tumorgenecity, invasion, metastasis, morphology (light microscopy, electron microscopy and immunohistochemistry), karyotype analysis and DNA content of the orthotopically transplanted tumors were studied. Results According to the new WHO classification of malignant lymphoma, a strain of liver metastasis model of human primary colonic lymphoma (non-Hodgkin's, B cell) in nude mice by orthotopic transplantation (HCBL-0301), and a strain of high metastasis model of human primary rectal lymphoma (non-Hodgkin's, B cell) in nude mice by orthotopic transplantation (HRBL-0302) were successfully screened from four cases of human primary colorectal lymphoma. Histopathology of transplanted tumors showed high grade non-Hodgkin's large B cell lymphoma. The cells were positive for CD19, CD20, CD22 and CD45, but negative for CD3 and CD7. The number of chromosome was between 55 and 69. DNA index (DI) was 1.59~1.71 (i.e. heteroploid). So far, HCBL-0301 and HRBL-0302 had been passaged for 31 and 27 generations in nude mice, respectively, and transplantation was successful in 326 nude mice. Since the third generation, both the growth rate of transplantation and rate of resuscitation after being thawed from liquid nitrogen cryopreservation were 100%. In HCBL-0301, metastasis to the right lobe of liver was most common and metastatic rate was 100%; additionally, rates metastasis to of lymph node and peritoneal seeding were 67.4%. In HRBL-0302, metastasis to the left and right lobes of liver was most common with metastasis rate of 63.7%, and rates of metastasis to lymph node and peritoneal seeding were 56.4%. Transplanted human primary colorectal lymphoma could autonomously and invasively grow in the colorectum of nude mice, with occurrence of hematogenic, lymph node and implantation metastases. Conclusions The study successfully replicated high metastasis models of human primary colorectal lymphoma in nude mice by orthotopic transplantation. HCBL-0301 and HRBL-0302 models can be used in the research on pathogenesis, mechanism of invasion and metastasis and experimental therapy of human primary colorectal lymphoma.