Mouse plasmacytoma: an experimental model of human multiple myeloma

Abstract

BACKGROUND AND OBJECTIVES: There is no ideal animal model for human multiple myeloma (MM). All the models resemble the human disease in some respect, but none of them fulfils all the criteria of a perfect animal model. EVIDENCE AND INFORMATION SOURCES: The pristane oil (2,6,10,12-tetramethylpentadecane)-induced mouse plasmacytoma (MPC) model is the most widely used and accepted model and has provided the most data on plasmacytomagenesis so far. This model gives the opportunity to study the role of c-myc dysregulations, the mechanisms leading to cytogenetic changes involving Ig genes, the role of chronic inflammatory factors, the role of interleukin-6 (IL-6), insulin-like growth factor-I, prostaglandins, as well as signal transduction pathways in the neoplastic process. Therapeutic agents have been successfully tested. Although MPC growth is usually restricted to the peritoneal environment, intraperitoneal injection of MPC cell suspensions can reproduce the disseminated characteristics of the human disease in recipients. The IL-6 transgene and knockout models are important tools for clarifying the role of IL-6 in the pathogenesis of MM. Transgenic mice and retroviral gene transfer facilitate the study of oncogenes in neoplastic transformation. Spontaneous development of plasmacytomas in C57BL/ KaLwRij aging mice has several advantages, mainly because the disseminated growth, the typical bone lesions and renal involvement resemble, in part, the human disease. Furthermore, this model has already proved useful in studies on the effect of bisphosphonate in the treatment of bone disease in MM. The severe combined immunodeficiency (SCID) mouse model is also very attractive. A disseminated-like disease can be reproduced in this model. Multiple osteolytic bone lesions and bone marrow involvement are generated, and conventional drugs applied in the treatment of human multiple myeloma have proven to be effective. Nevertheless, the immune system of SCID mice basically differs from that of a MM patient. PERSPECTIVES: Taken together, all these models have contributed to our understanding of MM, but demonstrate the opportuness of developing a more appropriate model of the human disease.