This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitsiades, C. S. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Mitsiades, C. S. Articles by Anderson, K. C.

Fluorescence Imaging of Multiple Myeloma Cells in a Clinically Relevant SCID/NOD in Vivo Model

Biologic and Clinical Implications¹

Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 [C. S. M., N. S. M., D. C., N. M., S. P. T., T. H., K. C. A.]; Departments of Medicine [C. S. M., N. S. M., D. C., N. M., S. P. T., T. H., K. C. A.] and Pathology [R. T. B.], Harvard Medical School, Boston, Massachusetts 02115; Cross Cancer Institute, University of Alberta, Edmonton, Alberta, T6G 1Z2 Canada [C. A. M., L. P.]; and Department of Surgery, University of California at San Diego, San Diego, California 92111 [R. M. H.]; and AntiCancer, Inc., San Diego, California 92111 [R. M. H.]

The in vivo preclinical testing of investigational therapies for multiple myeloma (MM) is hampered by the fact that models generated to recapitulate the development of diffuse skeletal lesions after i.v. injections of tumor cells do not allow for ready detection of the exact site(s) of lesions or for comprehensive monitoring of their progression. We therefore developed an in vivo MM model in severe combined immunodeficient/nonobese diabetic mice in which diffuse MM lesions developed after tail vein i.v. injection of human RPMI-8226/S MM cells stably transfected with a construct for green fluorescent protein (GFP). Using whole-body real-time fluorescence imaging to detect autofluorescent GFP⁺ MM cells (and confirming the sensitivity and specificity of these findings both histologically and by flow cytometric detection of GFP⁺ cells), we serially monitored, in a cohort of 75 mice, the development and progression of MM tumors. Their anatomical distribution and pathophysiological manifestations were consistent with the clinical course of MM in human patients, i.e., hallmarked by major involvement of the axial skeleton (e.g., spine, skull, and pelvis) and frequent development of paralysis secondary to spinal lesions without significant tumor spread to lungs, liver, spleen, or kidney. This model both recapitulates the diffuse bone disease of human MM and allows for serial whole-body visualization of its spatiotemporal progression. It therefore provides a valuable in vivo system to elucidate the molecular mechanisms underlying the marked osteotropism of MM, particularly for the axial skeleton, and for assessment of in vivo activity of novel anti-MM therapeutics.

This article has been cited by other articles:

				H. Rozemuller, E. van der Spek, L. H. Bogers-Boer, M. C. Zwart, V. Verweij, M. Emmelot, R. W. Groen, R. Spaapen, A. C. Bloem, H. M. Lokhorst, et al. A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect Haematologica, July 1, 2008; 93(7): 1049 - 1057. [Abstract] [Full Text] [PDF]

				B. O. Oyajobi, S. Munoz, R. Kakonen, P. J. Williams, A. Gupta, C. L. Wideman, B. Story, B. Grubbs, A. Armstrong, W. C. Dougall, et al. Detection of myeloma in skeleton of mice by whole-body optical fluorescence imaging Mol. Cancer Ther., June 1, 2007; 6(6): 1701 - 1708. [Abstract] [Full Text] [PDF]

				Y. Alsayed, H. Ngo, J. Runnels, X. Leleu, U. K. Singha, C. M. Pitsillides, J. A. Spencer, T. Kimlinger, J. M. Ghobrial, X. Jia, et al. Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)-dependent migration and homing in multiple myeloma Blood, April 1, 2007; 109(7): 2708 - 2717. [Abstract] [Full Text] [PDF]

				C. D. Peacock, Q. Wang, G. S. Gesell, I. M. Corcoran-Schwartz, E. Jones, J. Kim, W. L. Devereux, J. T. Rhodes, C. A. Huff, P. A. Beachy, et al. Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma PNAS, March 6, 2007; 104(10): 4048 - 4053. [Abstract] [Full Text] [PDF]

				W. Dalton and K. C. Anderson Synopsis of a Roundtable on Validating Novel Therapeutics for Multiple Myeloma. Clin. Cancer Res., November 15, 2006; 12(22): 6603 - 6610. [Abstract] [Full Text] [PDF]

				X. Xin, T. J. Abrams, P. W. Hollenbach, K. G. Rendahl, Y. Tang, Y. A. Oei, M. G. Embry, D. E. Swinarski, E. N. Garrett, N. K. Pryer, et al. CHIR-258 Is Efficacious in A Newly Developed Fibroblast Growth Factor Receptor 3-Expressing Orthotopic Multiple Myeloma Model in Mice. Clin. Cancer Res., August 15, 2006; 12(16): 4908 - 4915. [Abstract] [Full Text] [PDF]

				C. S. Mitsiades, N. S. Mitsiades, C. J. McMullan, V. Poulaki, A. L. Kung, F. E. Davies, G. Morgan, M. Akiyama, R. Shringarpure, N. C. Munshi, et al. Antimyeloma activity of heat shock protein-90 inhibition Blood, February 1, 2006; 107(3): 1092 - 1100. [Abstract] [Full Text] [PDF]

				T. Hideshima, D. Chauhan, P. Richardson, and K. C. Anderson Identification and Validation of Novel Therapeutic Targets for Multiple Myeloma J. Clin. Oncol., September 10, 2005; 23(26): 6345 - 6350. [Abstract] [Full Text] [PDF]

				T. Hideshima, P. L. Bergsagel, W. M. Kuehl, and K. C. Anderson Advances in biology of multiple myeloma: clinical applications Blood, August 1, 2004; 104(3): 607 - 618. [Abstract] [Full Text] [PDF]

				T. P. Thomas, M. T. Myaing, J. Y. Ye, K. Candido, A. Kotlyar, J. Beals, P. Cao, B. Keszler, A. K. Patri, T. B. Norris, et al. Detection and Analysis of Tumor Fluorescence Using a Two-Photon Optical Fiber Probe Biophys. J., June 1, 2004; 86(6): 3959 - 3965. [Abstract] [Full Text] [PDF]