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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1786-1793.
Prepublished online as a Blood First Edition Paper on May 10, 2005; DOI 10.1182/blood-2005-01-0049.
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NEOPLASIA
Wnts induce migration and invasion of myeloma plasma cells
Ya-Wei Qiang,
Katie Walsh,
Lei Yao,
Noemi Kedei,
Peter M. Blumberg,
Jeffrey S. Rubin,
John Shaughnessy, Jr, and
Stuart Rudikoff
From the Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD; the Experimental Transplantation and Immunology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD; the Laboratory of Cellular Carcinogenesis and Tumor Promotion, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD; and the Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR.
Multiple myeloma is an incurable form of lymphoid cancer characterized by accumulation of neoplastic plasma cells in the bone marrow cavity. Little is known about the mechanisms regulating myeloma cell movement within the bone marrow and metastasis to secondary sites. Herein, we identify multiple members of the wingless/int (Wnt) family as promoters of myeloma cell migration/invasion. Wnt-mediated migration was associated with the Wnt/RhoA pathway and did not necessitate signaling through  -catenin. Activation of both RhoA and members of the protein kinase C (PKC) family, including PKC , PKC, and PKCµ, were required for induction of migration. Activated RhoA and PKC, PKC, and PKCµ appear to assemble in macromolecular signaling complexes that are associated with the cell membrane. These results suggest that Wnt responsiveness of myeloma plasma cells may be a significant factor in disease progression. (Blood. 2005;106: 1786-1793)
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