Animal Models of Bone Metastasis

摘要: Ideal animal models of human cancers that metastasize to bone would reproduce the genetic and phenotypic changes occur with cancers. These include invasion, vascular spread bone, proliferation survival in marrow microenvironment subsequent modifications structure. In addition, such be reproducible progress rapidly permit timely investigations. Based on pathogenesis cancer rodents smaller mammals, this ideal may represent an unrealistic impractical goal. However, metastasis mimic selected aspects disease have been utilized refinements will continue developed. Because spontaneous animals is uncommon, most must derived experimentally. This limitation has resulted development specific unique stages metastasis. Thorough characterization these required their appropriate use as a representation disease. review includes information rather infrequent mammary prostate carcinoma, current uses other metastasis, recent developments better model There role for study well need refinement advance our understanding important manifestation oncogenesis. Cancer progression resulting metastases requires tissue invasion at site primary tumor, entry into vasculature, localization exit from microenvironment, modification structure function.1,2 The metastasis-enhancing suppressing genes, many which are currently being identified characterized using models. Bone (and suppressing) genes associated multiple cellular processes normally during mammalian development. regulate cell shape migration, interactions extracellular matrix stroma, angiogenesis, apoptosis, proliferation, proteins usually normal function (such hormones/cytokines activity). Although can readily by screening techniques (e.g., gene arrays), validation require sophisticated closely mirror pathophysiology humans. Because relatively artificial nature it necessary define what considered End-stage lesions identifiable reveal tumor modifies comparable clinically significant humans. Overt radiography or histopathology animals. quantification insensitive likely underestimates actual number metastases. For example, only detect severe not measure all fail induce lysis formation mineralized matrix. contrast, overestimation result newer highly sensitive techniques. polymerase chain reaction (PCR) cells arrested blood vessels quiescent develop metastases.3,4 Therefore, morphologic assessment confirm incidence each model. Animal tumors arise small mammals dogs cats), syngeneic transplantation spontaneously occurring rodent cancers, chemical induction strains rats mice, newly developed transgenic mouse models, xenografts lines immunodeficient nude mice rats, severely compromised [SCID] mice; Fig. 1). Xenografted injected, subcutaneously left ventricle heart, directly tibia femur. implanted orthotopic locations, fat pad, lungs, gland. Human ossicles induced subcutis serve implantation investigate nontraditional site.5,6 Animal used successfully select variants increased bone. Selection pressure maintained sustain desired phenotype. FIGURE 1 Animal domestic animals, cats; inbred hosts; chemically ...