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Cancer Chemotherapy and Pharmacology

, Volume 37, Issue 4, pp 305–316 | Cite as

Development of an orthotopic SCID mouse-human tumor xenograft model displaying the multidrug-resistant phenotype

  • W. T. Bellamy
  • Pamela Mendibles
  • Petra Bontje
  • Floyd Thompson
  • Lynne Richter
  • Ronald S. Weinstein
  • Thomas M. Grogan
  • T. M. Gorgan
ORIGINAL ARTICLE

Abstract

 Multiple myeloma is a plasma cell malignancy which is generally incurable in spite of a high initial response to chemotherapy. While animal models of myeloma are known, the recent developments of human xenografts in nude and SCID mice suggests a promising experimental model. The SCID model, in particular, holds promise because these animals readily accept hematopoietic and lymphoid transplantation and do not generally develop graft versus host reaction. We have developed two drug-resistant variants of the human multiple myeloma cell line ARH-77 by in vitro exposure to gradually increasing concentrations of doxorubicin (ARH-D60) or mitoxantrone (ARM-80). When injected into irradiated SCID mice, the ARH-D60 cell line grew in an orthotopic pattern with the development of osteolytic lesions. This is in contrast to the 8226/C1N human myeloma cell line which grows in a disseminated but nonorthotopic manner in the SCID mouse. Both the ARH-D60 and ARM-80 cell lines are resistant to doxorubicin and cross-resistant to mitoxantrone, vinca alkaloids, taxol and m-AMSA while maintaining sensitivity to antimetabolites and alkylating agents. Growth characteristics and cell cycle kinetics, including S-phase, were not altered in the resistant sublines. The ARH-D60 and ARM-80 cell lines both displayed a classic multidrug-resistance (MDR) phenotype which was partially reversed by the addition of verapamil. These two cell lines represent the first MDR human myeloma cell lines which have demonstrated an orthotopic growth pattern in the SCID mouse and thus may be of value in studying the pathophysiology of this disease.

Key words Multidrug resistance Multiple myeloma SCID mouse 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • W. T. Bellamy
    • 1
  • Pamela Mendibles
    • 1
  • Petra Bontje
    • 2
  • Floyd Thompson
    • 3
  • Lynne Richter
    • 1
  • Ronald S. Weinstein
    • 1
  • Thomas M. Grogan
  • T. M. Gorgan
    • 1
  1. 1.Department of Pathology, College of Medicine, University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724, USAUS
  2. 2.Free University, Amsterdam, The NetherlandsNL
  3. 3.Arizona Cancer Center, University of Arizona, College of Medicine, Tucson, Arizona, USAUS

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