title: An orthotopic mouse model for chondrosarcoma of bone provides an in vivo tool for drug testing.
abstract: Chondrosarcoma is a malignant cartilaginous tumor of the bone. Recently, mutations in isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) were identified in central chondrosarcomas. As chondrosarcomas are notoriously resistant to conventional treatment modalities, the need for model systems to screen new treatment options is high. We used two chondrosarcoma cell lines (CH2879 and SW1353) to generate a bioluminescent orthotopic chondrosarcoma mouse model. Cell lines were stably transduced with a lentiviral luciferase expression vector, and after clonal selection, luciferase-expressing clones were subcutaneously and orthotopically implanted in nude mice. Mice injected with CH2879 cells were treated with doxorubicin over a period of 6 weeks. Both cell lines resulted in tumor growth. CH2879 tumors were consistently larger than SW1353 tumors. No difference in size could be observed between subcutaneous and orthotopic tumors. Tumor growth could be monitored over time through assessment of luciferase activity, without harming the mice. Using this model, we show that doxorubicin does not have a significant effect on in vivo tumor growth. We describe an orthotopic chondrosarcoma mouse model that can be used to test new treatment strategies evolving from in vitro research.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.
authors.forename: Jolieke G
authors.initials: JG
authors.lastname: van Oosterwijk
authors.forename: Jacqueline R M
authors.initials: JR
authors.lastname: Plass
authors.forename: Danielle
authors.initials: D
authors.lastname: Meijer
authors.forename: Ivo
authors.initials: I
authors.lastname: Que
authors.forename: Marcel
authors.initials: M
authors.lastname: Karperien
authors.forename: Judith V M G
authors.initials: JV
authors.lastname: Bovée
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017211:Treatment Failure; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin