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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2015-2023. Prepublished online as a Blood First Edition Paper on December 6, 2007; DOI 10.1182/blood-2007-04-087841. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-04-087841v1 111/4/2015    most recent 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 Dimberg, A. Articles by Claesson-Welsh, L. Search for Related Content PubMed PubMed Citation Articles by Dimberg, A. Articles by Claesson-Welsh, L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY B-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis Anna Dimberg1, Svetlana Rylova1, Lothar C. Dieterich1, Anna-Karin Olsson1, Petter Schiller1, Charlotte Wikner1, Svante Bohman1, Johan Botling1, Agneta Lukinius1, Eric F. Wawrousek2, and Lena Claesson-Welsh1 1 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; and 2 National Eye Institute, National Institutes of Health, Bethesda, MD Selective targeting of endothelial cells in tumor vessels requires delineation of key molecular events in formation and survival of blood vessels within the tumor microenvironment. To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in antiangiogenic tumor therapy. The molecular chaperone B-crystallin was identified as specifically induced with regard to expression level, modification by serine phosphorylation, and subcellular localization during tubular morphogenesis of endothelial cells. Small interfering RNA–mediated knockdown of B-crystallin expression did not affect endothelial proliferation but led to attenuated tubular morphogenesis, early activation of proapoptotic caspase-3, and increased apoptosis. B-crystallin was expressed in a subset of human tumor vessels but not in normal capillaries. Tumors grown in B-crystallin–/– mice were significantly less vascularized than wild-type tumors and displayed increased areas of apoptosis/necrosis. Importantly, tumor vessels in B-crystallin–/– mice were leaky and showed signs of caspase-3 activation and extensive apoptosis. Ultrastructural analyses showed defective vessels partially devoid of endothelial lining. These data strongly implicate B-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis. Hereby we identify the small heat shock protein family as a novel class of angiogenic modulators. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: New entry for angiostatic cancer treatment Arjan W. Griffioen Blood 2008 111: 1755-1756. [Full Text] [PDF] This article has been cited by other articles: R. Ria, K. Todoerti, S. Berardi, A. M. L. Coluccia, A. De Luisi, M. Mattioli, D. Ronchetti, F. Morabito, A. Guarini, M. T. Petrucci, et al. Gene Expression Profiling of Bone Marrow Endothelial Cells in Patients with Multiple Myeloma Clin. Cancer Res., September 1, 2009; 15(17): 5369 - 5378. [Abstract] [Full Text] [PDF] S. Mellberg, A. Dimberg, F. Bahram, M. Hayashi, E. Rennel, A. Ameur, J. O. Westholm, E. Larsson, P. Lindahl, M. J. Cross, et al. Transcriptional profiling reveals a critical role for tyrosine phosphatase VE-PTP in regulation of VEGFR2 activity and endothelial cell morphogenesis FASEB J, May 1, 2009; 23(5): 1490 - 1502. [Abstract] [Full Text] [PDF] J. Zhang, J. Li, C. Huang, L. Xue, Y. Peng, Q. Fu, L. Gao, J. Zhang, and W. Li Targeted Knockout of the Mouse {beta}B2-crystallin Gene (Crybb2) Induces Age-Related Cataract Invest. Ophthalmol. Vis. Sci., December 1, 2008; 49(12): 5476 - 5483. [Abstract] [Full Text] [PDF] T. Matsumoto, P. Schiller, L. C. Dieterich, F. Bahram, Y. Iribe, U. Hellman, C. Wikner, G. Chan, L. Claesson-Welsh, and A. Dimberg Ninein Is Expressed in the Cytoplasm of Angiogenic Tip-Cells and Regulates Tubular Morphogenesis of Endothelial Cells Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2123 - 2130. [Abstract] [Full Text] [PDF]

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