The involvement of stromal derived factor 1α in homing and progression of multiple myeloma in the 5TMM model

Eline Menu, Kewal Asosingh, Stefano Indraccolo, Hendrik De Raeve, Ivan Van Riet, Els Van Valckenborgh, Isabelle Vande Broek, Nobutaka Fujii, Hirokazu Tamamura, Ben Van Camp, Karin Vanderkerken

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Objectives. Multiple myeloma (MM) is a lethal plasma cell cancer characterized by the monoclonal growth of cells in the bone marrow. To reach the bone marrow, MM cells need to be attracted by chemokines. Recently, it has been shown that chemokines can also be involved in the growth of several cancer types. Stromal cell derived factor 1α (SDF1α) or CXCL12 is known to play an important role as a chemokine for hematopoietic progenitor cells and human MM cells. We studied the effects of SDF1α in the 5TMM murine model. Design and Methods. The in vitro effects of SDF1α were analyzed by gelatin zymography, adhesion, migration, proliferation, and chemoinvasion assays and by blockade with the CXCR4 inhibitor, 4F-benzoyl-TN14003. In vivo, diseased mice were treated with either vehicle or 4F-benzoyl-TN14003. Results. In vitro SDF1α was capable of attracting both 5T2MM and 5T33MM cells and inducing a 1.6-fold increase in MMP9 production by the 5TMM cells, which was correlated with an increased invasive capacity. In addition, SDF1α induced a 20% increase in DNA synthesis in the 5TMM cells. All these effects could be blocked by the CXCR4 inhibitor, 4F-benzoyl-TN14003. An in vivo study in the 5T33MM model showed that blocking CXCR4 led to a 20% reduction in bone marrow tumor load. Interpretation and Conclusions. These data demonstrate that SDF1α/CXCR4 is involved in the homing and the expansion of MM cells. Blocking CXCR4 could be useful in synergy with other anti-neoplastic treatments targeting the bone marrow microenvironment.

Original languageEnglish
Pages (from-to)605-612
Number of pages8
JournalHaematologica
Volume91
Issue number5
Publication statusPublished - May 2006

Keywords

  • Chemokines
  • Myeloma
  • SDf1α

ASJC Scopus subject areas

  • Hematology

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