Intratibial injection of human multiple myeloma cells in NOD/SCID IL-2Rγ(null) mice mimics human myeloma and serves as a valuable tool for the development of anticancer strategies.
BACKGROUND
We systematically analyzed multiple myeloma (MM) cell lines and patient bone marrow cells for their engraftment capacity in immunodeficient mice and validated the response of the resulting xenografts to antimyeloma agents.


METHODS
Using flow cytometry and near infrared fluorescence in-vivo-imaging, growth kinetics of MM cell lines L363 and RPMI8226 and patient bone marrow cells were investigated with use of a murine subcutaneous bone implant, intratibial and intravenous approach in NOD/SCID, NOD/SCID treated with CD122 antibody and NOD/SCID IL-2Rγ(null) mice (NSG).


RESULTS
Myeloma growth was significantly increased in the absence of natural killer cell activity (NSG or αCD122-treated NOD/SCID). Comparison of NSG and αCD122-treated NOD/SCID revealed enhanced growth kinetics in the former, especially with respect to metastatic tumor sites which were exclusively observed therein. In NSG, MM cells were more tumorigenic when injected intratibially than intravenously. In NOD/SCID in contrast, the use of juvenile long bone implants was superior to intratibial or intravenous cancer cell injection. Using the intratibial NSG model, mice developed typical disease symptoms exclusively when implanted with human MM cell lines or patient-derived bone marrow cells, but not with healthy bone marrow cells nor in mock-injected animals. Bortezomib and dexamethasone delayed myeloma progression in L363- as well as patient-derived MM cell bearing NSG. Antitumor activity could be quantified via flow cytometry and in vivo imaging analyses.


CONCLUSIONS
Our results suggest that the intratibial NSG MM model mimics the clinical situation of the disseminated disease and serves as a valuable tool in the development of novel anticancer strategies.
Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany ; Department for Invivo Tumorbiology, Oncotest, Freiburg, Germany.
Julia
J
Schueler
Dagmar
D
Wider
Kerstin
K
Klingner
Gabrielle M
GM
Siegers
Annette M
AM
May
Ralph
R
Wäsch
Heinz-Herbert
HH
Fiebig
Monika
M
Engelhardt
D000818:Animals; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D011719:Pyrazines / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000172:deficiency* / Q000235:genetics
D001897:Boronic Acids; D011719:Pyrazines; D015375:Receptors, Interleukin-2; D000069286:Bortezomib; D003907:Dexamethasone