title: A clinically relevant SCID-hu in vivo model of human multiple myeloma.
abstract: We developed a novel in vivo multiple myeloma (MM) model by engrafting the interleukin 6 (IL-6)-dependent human MM cell line INA-6 into severe combined immunodeficiency (SCID) mice previously given implants of a human fetal bone chip (SCID-hu mice). INA-6 cells require either exogenous human IL-6 (huIL-6) or bone marrow stromal cells (BMSCs) to proliferate in vitro. In this model, we monitored the in vivo growth of INA-6 cells stably transduced with a green fluorescent protein (GFP) gene (INA-6GFP+ cells). INA-6 MM cells engrafted in SCID-hu mice but not in SCID mice that had not been given implants of human fetal bone. The level of soluble human IL-6 receptor (shuIL-6R) in murine serum and fluorescence imaging of host animals were sensitive indicators of tumor growth. Dexamethasone as well as experimental drugs, such as Atiprimod and B-B4-DM1, were used to confirm the utility of the model for evaluation of anti-MM agents. We report that this model is highly reproducible and allows for evaluation of investigational drugs targeting IL-6-dependent MM cells in the human bone marrow (huBM) milieu.
authors.affiliation: Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and VA Boston Healthcare System, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.forename: Paola
authors.initials: P
authors.lastname: Neri
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Carrasco
authors.forename: Renate
authors.initials: R
authors.lastname: Burger
authors.forename: Victor S
authors.initials: VS
authors.lastname: Goldmacher
authors.forename: Robert
authors.initials: R
authors.lastname: Fram
authors.forename: Vidit
authors.initials: V
authors.lastname: Munshi
authors.forename: Masood A
authors.initials: MA
authors.lastname: Shammas
authors.forename: Laurence
authors.initials: L
authors.lastname: Catley
authors.forename: Gary S
authors.initials: GS
authors.lastname: Jacob
authors.forename: Salvatore
authors.initials: S
authors.lastname: Venuta
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
mesh_terms: D000818:Animals; D016025:Bone Transplantation; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D009368:Neoplasm Transplantation; D019947:Receptors, Interleukin-6 / Q000097:blood; D011994:Recombinant Proteins / Q000235:genetics; D013141:Spiro Compounds / Q000494:pharmacology; D014161:Transduction, Genetic; D014183:Transplantation, Heterologous
chemical_list: D000922:Immunotoxins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D013141:Spiro Compounds; C099015:azaspirane; D049452:Green Fluorescent Proteins; D003907:Dexamethasone