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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Podar, K. Articles by Anderson, K. C. Search for Related Content PubMed PubMed Citation Articles by Podar, K. Articles by Anderson, K. C. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 July 2001, Vol. 98, No. 2, pp. 428-435 NEOPLASIA Vascular endothelial growth factor triggers signaling cascades mediating multiple myeloma cell growth and migration Klaus Podar, Yu-Tzu Tai, Faith E. Davies, Suzanne Lentzsch, Martin Sattler, Teru Hideshima, Boris K. Lin, Deepak Gupta, Yoshihito Shima, Dharminder Chauhan, Constantine Mitsiades, Noopur Raje, Paul Richardson, and Kenneth C. Anderson From the Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA. Multiple myeloma (MM) remains incurable, with a median survival of 3 to 4 years. This study shows direct effects of vascular endothelial growth factor (VEGF) upon MM and plasma cell leukemia (PCL) cells. The results indicate that VEGF triggers tumor cell proliferation via a protein kinase C (PKC)-independent Raf-1-MEK-extracellular signal-regulated protein kinase pathway, and migration via a PKC-dependent pathway. These observations provide the framework for novel therapeutic strategies targeting VEGF signaling cascades in MM. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. KROPFF, J. KIENAST, G. BISPING, W. E. BERDEL, B. GASCHLER-MARKEFSKI, P. STOPFER, M. STEFANIC, and G. MUNZERT An Open-label Dose-escalation Study of BIBF 1120 in Patients with Relapsed or Refractory Multiple Myeloma Anticancer Res, October 1, 2009; 29(10): 4233 - 4238. [Abstract] [Full Text] [PDF] J. Zhang, M. Sattler, G. Tonon, C. Grabher, S. Lababidi, A. Zimmerhackl, M. S. Raab, S. Vallet, Y. Zhou, M.-A. Cartron, et al. Targeting Angiogenesis via a c-Myc/Hypoxia-Inducible Factor-1{alpha}-Dependent Pathway in Multiple Myeloma Cancer Res., June 15, 2009; 69(12): 5082 - 5090. [Abstract] [Full Text] [PDF] M. Koldehoff, D. W. Beelen, and A. H. 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The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma PNAS, December 19, 2006; 103(51): 19478 - 19483. [Abstract] [Full Text] [PDF] M. Li, S. Cortez, T. Nakamachi, V. Batuman, and A. Arimura Pituitary Adenylate Cyclase-Activating Polypeptide Is a Potent Inhibitor of the Growth of Light Chain-Secreting Human Multiple Myeloma Cells. Cancer Res., September 1, 2006; 66(17): 8796 - 8803. [Abstract] [Full Text] [PDF] F. A. Piazza, M. Ruzzene, C. Gurrieri, B. Montini, L. Bonanni, G. Chioetto, G. Di Maira, F. Barbon, A. Cabrelle, R. Zambello, et al. Multiple myeloma cell survival relies on high activity of protein kinase CK2 Blood, September 1, 2006; 108(5): 1698 - 1707. [Abstract] [Full Text] [PDF] M. A. Rizvi, K. Ghias, K. M. Davies, C. Ma, F. Weinberg, H. G. Munshi, N. L. Krett, and S. T. Rosen Enzastaurin (LY317615), a protein kinase C{beta} inhibitor, inhibits the AKT pathway and induces apoptosis in multiple myeloma cell lines. Mol. Cancer Ther., July 1, 2006; 5(7): 1783 - 1789. [Abstract] [Full Text] [PDF] G. Bisping, M. Kropff, D. Wenning, B. Dreyer, S. Bessonov, F. Hilberg, G. J. Roth, G. Munzert, M. Stefanic, M. Stelljes, et al. Targeting receptor kinases by a novel indolinone derivative in multiple myeloma: abrogation of stroma-derived interleukin-6 secretion and induction of apoptosis in cytogenetically defined subgroups Blood, March 1, 2006; 107(5): 2079 - 2089. [Abstract] [Full Text] [PDF] N. Yanamandra, N. M. Colaco, N. A. Parquet, R. W. Buzzeo, D. Boulware, G. Wright, L. E. Perez, W. S. Dalton, and D. M. Beaupre Tipifarnib and Bortezomib Are Synergistic and Overcome Cell Adhesion-Mediated Drug Resistance in Multiple Myeloma and Acute Myeloid Leukemia Clin. Cancer Res., January 15, 2006; 12(2): 591 - 599. [Abstract] [Full Text] [PDF] A. M. Roccaro, T. Hideshima, N. Raje, S. Kumar, K. Ishitsuka, H. Yasui, N. Shiraishi, D. Ribatti, B. Nico, A. Vacca, et al. Bortezomib Mediates Antiangiogenesis in Multiple Myeloma via Direct and Indirect Effects on Endothelial Cells Cancer Res., January 1, 2006; 66(1): 184 - 191. [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] M. Altun, P. J. Galardy, R. Shringarpure, T. Hideshima, R. LeBlanc, K. C. Anderson, H. L. Ploegh, and B. M. Kessler Effects of PS-341 on the Activity and Composition of Proteasomes in Multiple Myeloma Cells Cancer Res., September 1, 2005; 65(17): 7896 - 7901. [Abstract] [Full Text] [PDF] Y.-W. Qiang, K. Walsh, L. Yao, N. Kedei, P. M. Blumberg, J. S. Rubin, J. Shaughnessy Jr, and S. Rudikoff Wnts induce migration and invasion of myeloma plasma cells Blood, September 1, 2005; 106(5): 1786 - 1793. [Abstract] [Full Text] [PDF] H M. Prince, L. Mileshkin, A. Roberts, V. Ganju, C. Underhill, J. Catalano, R. Bell, J. F. Seymour, D. Westerman, P. J. Simmons, et al. A Multicenter Phase II Trial of Thalidomide and Celecoxib for Patients with Relapsed and Refractory Multiple Myeloma Clin. Cancer Res., August 1, 2005; 11(15): 5504 - 5514. [Abstract] [Full Text] [PDF] K. J. Till, D. G. Spiller, R. J. Harris, H. Chen, M. Zuzel, and J. C. Cawley CLL, but not normal, B cells are dependent on autocrine VEGF and {alpha}4{beta}1 integrin for chemokine-induced motility on and through endothelium Blood, June 15, 2005; 105(12): 4813 - 4819. [Abstract] [Full Text] [PDF] M. Hamasaki, T. Hideshima, P. Tassone, P. Neri, K. Ishitsuka, H. Yasui, N. Shiraishi, N. Raje, S. Kumar, D. H. Picker, et al. Azaspirane (N-N-diethyl-8,8-dipropyl-2-azaspiro [4.5] decane-2-propanamine) inhibits human multiple myeloma cell growth in the bone marrow milieu in vitro and in vivo Blood, June 1, 2005; 105(11): 4470 - 4476. [Abstract] [Full Text] [PDF] L. Vincent, D. K. Jin, M. A. Karajannis, K. Shido, A. T. Hooper, W. K. Rashbaum, B. Pytowski, Y. Wu, D. J. Hicklin, Z. Zhu, et al. Fetal Stromal-Dependent Paracrine and Intracrine Vascular Endothelial Growth Factor-A/Vascular Endothelial Growth Factor Receptor-1 Signaling Promotes Proliferation and Motility of Human Primary Myeloma Cells Cancer Res., April 15, 2005; 65(8): 3185 - 3192. [Abstract] [Full Text] [PDF] K. Podar and K. C. Anderson The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications Blood, February 15, 2005; 105(4): 1383 - 1395. [Abstract] [Full Text] [PDF] M. Chatterjee, T. Stuhmer, P. Herrmann, K. Bommert, B. Dorken, and R. C. Bargou Combined disruption of both the MEK/ERK and the IL-6R/STAT3 pathways is required to induce apoptosis of multiple myeloma cells in the presence of bone marrow stromal cells Blood, December 1, 2004; 104(12): 3712 - 3721. [Abstract] [Full Text] [PDF] T. Hayashi, T. Hideshima, A. N. Nguyen, O. Munoz, K. Podar, M. Hamasaki, K. Ishitsuka, H. Yasui, P. Richardson, S. Chakravarty, et al. Transforming Growth Factor {beta} Receptor I Kinase Inhibitor Down-Regulates Cytokine Secretion and Multiple Myeloma Cell Growth in the Bone Marrow Microenvironment Clin. Cancer Res., November 15, 2004; 10(22): 7540 - 7546. [Abstract] [Full Text] [PDF] S. Le Gouill, K. Podar, M. Amiot, T. Hideshima, D. Chauhan, K. Ishitsuka, S. Kumar, N. Raje, P. G. Richardson, J.-L. Harousseau, et al. VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis Blood, November 1, 2004; 104(9): 2886 - 2892. [Abstract] [Full Text] [PDF] K. Podar, R. Shringarpure, Y.-T. Tai, M. Simoncini, M. Sattler, K. Ishitsuka, P. G. Richardson, T. Hideshima, D. Chauhan, and K. C. Anderson Caveolin-1 Is Required for Vascular Endothelial Growth Factor-Triggered Multiple Myeloma Cell Migration and Is Targeted by Bortezomib Cancer Res., October 15, 2004; 64(20): 7500 - 7506. [Abstract] [Full Text] [PDF] S. Kumar, T. E. Witzig, M. Timm, J. Haug, L. Wellik, T. K. Kimlinger, P. R. Greipp, and S. V. Rajkumar Bone marrow angiogenic ability and expression of angiogenic cytokines in myeloma: evidence favoring loss of marrow angiogenesis inhibitory activity with disease progression Blood, August 15, 2004; 104(4): 1159 - 1165. [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] K. Podar, G. Mostoslavsky, M. Sattler, Y.-T. Tai, T. Hayashi, L. P. Catley, T. Hideshima, R. C. Mulligan, D. Chauhan, and K. C. Anderson Critical Role for Hematopoietic Cell Kinase (Hck)-mediated Phosphorylation of Gab1 and Gab2 Docking Proteins in Interleukin 6-induced Proliferation and Survival of Multiple Myeloma Cells J. Biol. Chem., May 14, 2004; 279(20): 21658 - 21665. [Abstract] [Full Text] [PDF] K. Podar, L. P. Catley, Y.-T. Tai, R. Shringarpure, P. Carvalho, T. Hayashi, R. Burger, R. L. Schlossman, P. G. Richardson, L. N. Pandite, et al. GW654652, the pan-inhibitor of VEGF receptors, blocks the growth and migration of multiple myeloma cells in the bone marrow microenvironment Blood, May 1, 2004; 103(9): 3474 - 3479. [Abstract] [Full Text] [PDF] D. Chauhan, G. Li, K. Podar, T. Hideshima, R. Shringarpure, L. Catley, C. Mitsiades, N. Munshi, Y. T. Tai, N. Suh, et al. The bortezomib/proteasome inhibitor PS-341 and triterpenoid CDDO-Im induce synergistic anti-multiple myeloma (MM) activity and overcome bortezomib resistance Blood, April 15, 2004; 103(8): 3158 - 3166. [Abstract] [Full Text] [PDF] J.-L. Harousseau, J. Shaughnessy Jr., and P. Richardson Multiple Myeloma Hematology, January 1, 2004; 2004(1): 237 - 256. [Abstract] [Full Text] [PDF] J. E. Lancet and J. E. Karp Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy Blood, December 1, 2003; 102(12): 3880 - 3889. [Abstract] [Full Text] [PDF] A. Vacca, R. Ria, F. Semeraro, F. Merchionne, M. Coluccia, A. Boccarelli, C. Scavelli, B. Nico, A. Gernone, F. Battelli, et al. Endothelial cells in the bone marrow of patients with multiple myeloma Blood, November 1, 2003; 102(9): 3340 - 3348. [Abstract] [Full Text] [PDF] T. Hayashi, T. Hideshima, M. Akiyama, N. Raje, P. Richardson, D. Chauhan, and K. C. Anderson Ex vivo induction of multiple myeloma-specific cytotoxic T lymphocytes Blood, August 15, 2003; 102(4): 1435 - 1442. [Abstract] [Full Text] [PDF] L. C. Platanias Map kinase signaling pathways and hematologic malignancies Blood, June 15, 2003; 101(12): 4667 - 4679. [Abstract] [Full Text] [PDF] G. H. 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Prognostic value of angiogenesis in solitary bone plasmacytoma Blood, March 1, 2003; 101(5): 1715 - 1717. [Abstract] [Full Text] [PDF] K. Podar, Y.-T. Tai, C. E. Cole, T. Hideshima, M. Sattler, A. Hamblin, N. Mitsiades, R. L. Schlossman, F. E. Davies, G. J. Morgan, et al. Essential Role of Caveolae in Interleukin-6- and Insulin-like Growth Factor I-triggered Akt-1-mediated Survival of Multiple Myeloma Cells J. Biol. Chem., February 14, 2003; 278(8): 5794 - 5801. [Abstract] [Full Text] [PDF] T. Hideshima, M. Akiyama, T. Hayashi, P. Richardson, R. Schlossman, D. Chauhan, and K. C. Anderson Targeting p38 MAPK inhibits multiple myeloma cell growth in the bone marrow milieu Blood, January 15, 2003; 101(2): 703 - 705. [Abstract] [Full Text] [PDF] R. E. Bachelder, M. A. Wendt, and A. M. Mercurio Vascular Endothelial Growth Factor Promotes Breast Carcinoma Invasion in an Autocrine Manner by Regulating the Chemokine Receptor CXCR4 Cancer Res., December 15, 2002; 62(24): 7203 - 7206. 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Podar, et al. 2-Methoxyestradiol overcomes drug resistance in multiple myeloma cells Blood, August 28, 2002; 100(6): 2187 - 2194. [Abstract] [Full Text] [PDF] T. Hayashi, T. Hideshima, M. Akiyama, P. Richardson, R. L. Schlossman, D. Chauhan, N. C. Munshi, S. Waxman, and K. C. Anderson Arsenic Trioxide Inhibits Growth of Human Multiple Myeloma Cells in the Bone Marrow Microenvironment Mol. Cancer Ther., August 1, 2002; 1(10): 851 - 860. [Abstract] [Full Text] [PDF] S. V. Rajkumar, R. A. Mesa, R. Fonseca, G. Schroeder, M. F. Plevak, A. Dispenzieri, M. Q. Lacy, J. A. Lust, T. E. Witzig, M. A. Gertz, et al. Bone Marrow Angiogenesis in 400 Patients with Monoclonal Gammopathy of Undetermined Significance, Multiple Myeloma, and Primary Amyloidosis Clin. Cancer Res., July 1, 2002; 8(7): 2210 - 2216. [Abstract] [Full Text] [PDF] A.-T. Brenne, T. Baade Ro, A. Waage, A. Sundan, M. Borset, and H. Hjorth-Hansen Interleukin-21 is a growth and survival factor for human myeloma cells Blood, May 15, 2002; 99(10): 3756 - 3762. [Abstract] [Full Text] [PDF] T. Hideshima, D. Chauhan, T. Hayashi, K. Podar, M. Akiyama, D. Gupta, P. Richardson, N. Munshi, and K. C. Anderson The Biological Sequelae of Stromal Cell-derived Factor-1{alpha} in Multiple Myeloma Mol. Cancer Ther., May 1, 2002; 1(7): 539 - 544. [Abstract] [Full Text] [PDF] S. Lentzsch, M. S. Rogers, R. LeBlanc, A. E. Birsner, J. H. Shah, A. M. Treston, K. C. Anderson, and R. J. D'Amato S-3-Amino-phthalimido-glutarimide Inhibits Angiogenesis and Growth of B-Cell Neoplasias in Mice Cancer Res., April 1, 2002; 62(8): 2300 - 2305. [Abstract] [Full Text] [PDF] M. A. Hussein Nontraditional Cytotoxic Therapies for Relapsed/Refractory Multiple Myeloma Oncologist, April 1, 2002; 7(90001): 20 - 29. [Abstract] [Full Text] [PDF] K. Podar, Y.-T. Tai, B. K. Lin, R. P. Narsimhan, M. Sattler, T. Kijima, R. Salgia, D. Gupta, D. Chauhan, and K. C. Anderson Vascular Endothelial Growth Factor-induced Migration of Multiple Myeloma Cells Is Associated with beta 1 Integrin- and Phosphatidylinositol 3-Kinase-dependent PKCalpha Activation J. Biol. Chem., March 1, 2002; 277(10): 7875 - 7881. [Abstract] [Full Text] [PDF] Y.-T. Tai, K. Podar, D. Gupta, B. Lin, G. Young, M. Akiyama, and K. C. Anderson CD40 activation induces p53-dependent vascular endothelial growth factor secretion in human multiple myeloma cells Blood, February 15, 2002; 99(4): 1419 - 1427. [Abstract] [Full Text] [PDF] K. C. Anderson, J. D. Shaughnessy Jr., B. Barlogie, J.-L. Harousseau, and G. D. Roodman Multiple Myeloma Hematology, January 1, 2002; 2002(1): 214 - 240. [Abstract] [Full Text] W. S. Dalton, P. L. Bergsagel, W. M. Kuehl, K. C. Anderson, and J. L. Harousseau Multiple Myeloma Hematology, January 1, 2001; 2001(1): 157 - 177. [Abstract] [Full Text] [PDF]

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