Abstract
Wnts comprise a family of secreted proteins that interact with receptors consisting of a Frizzled (Fz) family member alone or complexed with LDL receptor-related proteins (LRP5/6). Wnt signaling plays a crucial role in both development and differentiation, and activation of a ‘canonical’ Wnt pathway resulting in β-catenin stabilization is associated with several types of human cancers. To date, little is known about potential Wnt signaling in mature lymphocytes or lymphoid neoplasia. Herein, we have analysed Wnt signaling in mature B cells (lymphomas) and plasma cells (multiple myeloma). Both Fz and LRP5/6 mRNAs were expressed in myeloma lines, but LRP5/6 were not observed in lymphomas. In myelomas, a canonical Wnt signaling pathway was activated following treatment with Wnt-3a as assessed by accumulation of β-catenin, but β-catenin levels actually decreased in lymphoma cells. Wnt-3a treatment further led to striking morphological changes in myeloma cells accompanied by rearrangement of the actin cytoskeleton. Morphological changes were associated with a second Wnt pathway dependent on Rho activation. These results suggest that Wnt responsiveness is a stage-specific phenomenon in B-cell development and that the morphological changes associated with Wnt signaling may play a role in the motility and metastatic potential of myeloma cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Bataille R, Chappard D and Klein B . (1992). Hematol. Oncol. Clin. North Am., 6, 285–295.
Bergui L, Schena M, Gaidano G, Riva M and Caligaris-Cappio F . (1989). J. Exp. Med., 170, 613–618.
Brandon C, Eisenberg LM and Eisenberg CA . (2000). Blood, 96, 4132–4141.
Ferlin M, Noraz N, Hertogh C, Brochier J, Taylor N and Klein B . (2000). Br. J. Haematol., 111, 626–634.
Ge NL and Rudikoff S . (2000). Blood, 96, 4091–4095.
Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GCM, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, Paepe AD, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Jüppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, Boogaard M, Hul WV, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR and Warman ML . (2001). Cell, 107, 513–523.
Habas R, Kato Y and He X . (2001). Cell, 107, 843–854.
Hilbert DM, Kopf M, Mock BA, Kohler G and Rudikoff S . (1995). J. Exp. Med., 182, 243–248.
Ioannidis V, Beermann F, Clevers H and Held W . (2001). Nat. Immunol., 2, 691–697.
Ishizaki T, Uehata M, Tamechika I, Keel J, Nonomura K, Maekawa M and Narumiya S . (2000). Mol. Pharm., 57, 976–983.
Korinek V, Barker N, Morin P, van Wichen D, de Weger R, Kinzler K, Vogelstein B and Clevers H . (1997). Science, 275, 1784–1787.
Lattanzio G, Libert C, Aquilina M, Cappelletti M, Ciliberto G, Musiani P and Poli V . (1997). Am. J. Pathol., 151, 689–696.
Lee JS, Ishimoto A and Yanagawa S . (1999). J. Biol. Chem., 274, 21464–21470.
Little RD, Carulli JP, Del Mastro RG, Dupuis J, Osborne M, Folz C and Manning SP . (2002). Am. J. Hum. Genet., 70, 11–19.
Lu ZY, Brailly H, Wijdenes J, Bataille R, Rossi JF and Klein B . (1995). Blood, 86, 3123–3131.
Mao B, Wu W, Li Y, Hoppe D, Stannek P, Glinka A and Niehrs C . (2001). Nature, 411, 321–325.
McWhirter JR, Neuteboom ST, Wancewicz EV, Monia BP, Downing JR and Murre C . (1999). Proc. Natl. Acad. Sci. USA, 96, 11464–11469.
Miller J, Hocking A, Brown J and Moon R . (1999). Oncogene, 18, 7860–7872.
Niesvizky R and Warrell RJ . (1997). Cancer Invest., 15, 85–90.
Oosterwegel M, van de Wetering M, Timmerman J, Kruisbeek A, Destree O and Meijlink F . (1993). Development, 118, 439–448.
Peifer M and Polakis P . (2000). Science, 287, 1606–1609.
Pinson KI, Brennan J, Monkley S, Avery BJ and Skarnes WC . (2000). Nature, 407, 535–538.
Polakis P . (2000). Genes Dev., 14, 1837–1851.
Qiang Y, Kopantzev E and Rudikoff S . (2002). Blood, 99, 4138–4146.
Ren X, Kiosses W and Schwartz M . (1999). EMBO J., 18, 578–585.
Reya T, O’Riordan M, Okamura R, Devaney E, Willert K, Nusse R and Grosschedl R . (2000). Immunity, 13, 15–24.
Semenov MV and Snyder M . (1997). Genomics, 42, 302–310.
Semenov M, Tamai K, Brott B, Kuhl M, Sokol S and He X . (2001). Curr. Biol., 11, 951–961.
Shibamoto S, Higano K, Takada R, Ito F, Takeichi M and Takada S . (1998). Genes Cells, 3, 659–670
Tamai K, Semenov M, Kato Y, Spokony R, Liu C, Katsuyama Y, Hess F, Saint-Jeannet JP and He X . (2000). Nature, 407, 530–535.
Uren A, Reichsman F, Anest V, Taylor WG, Muraiso K, Bottaro DP, Cumberledge S and Rubin JS . (2000). J. Biol. Chem., 275, 4374–4382.
Van de Wetering M, Castrop J, Korinek V and Clevers H . (1996). Mol. Cell Biol., 16, 745–752.
Wehrli M, Dougan ST, Caldwell K, O’Keefe L, Schwartz S, Vaizel-Ohayon D, Schejter E, Tomlinson A and DiNardo S . (2000). Nature, 407, 527–530.
Winter C, Wang B, Ballew A, Royou A, Karess R, Axelrod J and Luo L . (2001). Cell, 105, 81–91
Wodarz A and Nusse R . (1998). Annu. Rev. Cell Dev. Biol., 14, 59–88.
Yamane T, Kunisada T, Tsukamoto H, Yamazaki H, Niwa H, Takada S and Hayashi SI . (2001). J. Immunol., 167, 765–772.
Yanagawa S, van Leeuwen F, Wodarz A, Klingensmith J and Nusse R . (1995). Genes Dev., 9, 1087–1097.
Zhang XG, Gaillard JP, Robillard N, Lu ZY, Gu ZJ, Jourdan M, Boiron JM, Bataille R and Klein B . (1994). Blood, 83, 3654–3663.
Zhurinsky J, Shtutman M and Ben-Ze’ev A . (2000). J. Cell Sci., 113, 3127–3139.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is a United States Government Work Paper as defined by the US Copyright Act
Rights and permissions
About this article
Cite this article
Qiang, YW., Endo, Y., Rubin, J. et al. Wnt signaling in B-cell neoplasia. Oncogene 22, 1536–1545 (2003). https://doi.org/10.1038/sj.onc.1206239
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1206239
Keywords
This article is cited by
-
Immunomodulatory effects of heat stress and lipopolysaccharide on the bursal transcriptome in two distinct chicken lines
BMC Genomics (2018)
-
Wnt signaling in multiple myeloma: a central player in disease with therapeutic potential
Journal of Hematology & Oncology (2018)
-
An Evidence-Based Approach to Myeloma Bone Disease
Current Hematologic Malignancy Reports (2017)
-
Wnt3a: functions and implications in cancer
Chinese Journal of Cancer (2015)
-
WNT signalling pathways as therapeutic targets in cancer
Nature Reviews Cancer (2013)