Establishment of a Novel Bladder Cancer Xenograft Model in Humanized Immunodeficient Mice

• Published in: Cellular physiology and biochemistry Vol. 37; no. 4; pp. 1355 - 1368
• Main Authors: Gong, Zhen, Xu, Hanzi, Su, Yiping, Wu, Wangfei, Hao, Lin, Han, Conghui
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Cell Physiol Biochem Press GmbH & Co KG 01.01.2015
• Subjects: Animal model; Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bladder cancer; CD3 Complex - genetics; CD3 Complex - metabolism; Cell Line, Tumor; Cytokines - analysis; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gamma Rays; Humans; Immunotherapy; Lymphocyte Transfusion; Lymphocytes - cytology; Mice; Mice, SCID; Original Paper; Real-Time Polymerase Chain Reaction; Severe combined immunodeficient mice; Spleen - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transplantation, Heterologous; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Animal model; Severe combined immunodeficient mice; Bladder cancer; Immunotherapy
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000430401

Background/Aims: The aim of this study was to develop a novel model by transplanting human bladder cancer xenografts into humanized immunodeficient mice (SCID). Methods: The animals first underwent sublethal irradiation and then were subjected to simultaneous transplantation of human lymphocytes (5 × 10 7 cells/mouse i.p.) and human bladder cancer cells (3 × 10 6 cells/mouse s.c.). Results: The xenografts developed in all 12 mice that had received bladder cancer BIU-87 cells, and the tumor specimens were evaluated histologically. All 6 model mice expressed human CD3 mRNA and/or protein in the peripheral blood, spleens and xenografts. The mean proportion of human CD3 + cells was 19% with a level of human IgG 532.4µ/ml in the peripheral blood at Week 6 after transplant inoculation. The re-constructed human immune system in these mice was confirmed to be functional by individual in vitro testing of their proliferative, secretory and cytotoxic responses. Conclusion: The successful engraftment of the human bladder cancer xenografts and the establishment of the human immune system in our in vivo model described here may provide a useful tool for the development of novel therapeutic strategies targeting at bladder cancer.