J. Exp. Med., Volume 188, Number 12, December 21, 1998 2349-2356

Vasostatin, a Calreticulin Fragment, Inhibits Angiogenesis and Suppresses Tumor Growth

By Sandra E. Pike,^* Lei Yao,^* Karen D. Jones,^* Barry Cherney,^* Ettore Appella, Kazuyasu Sakaguchi, Hira Nakhasi,^* Julie Teruya-Feldstein,^§ Peter Wirth, Ghanshyam Gupta,^* and Giovanna Tosato^*

From the ^* Center for Biologics Evaluation and Research, Rockville, Maryland 20852; and the  Laboratory of Cell Biology, the ^§ Laboratory of Pathology, and the  Laboratory of Experimental Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892

An endothelial cell inhibitor was purified from supernatant of an Epstein-Barr virus-immortalized cell line and identified as fragments of calreticulin. The purified recombinant NH₂-terminal domain of calreticulin (amino acids 1-180) inhibited the proliferation of endothelial cells, but not cells of other lineages, and suppressed angiogenesis in vivo. We have named this NH₂-terminal domain of calreticulin vasostatin. When inoculated into athymic mice, vasostatin significantly reduced growth of human Burkitt lymphoma and human colon carcinoma. Compared with other inhibitors of angiogenesis, vasostatin is a small, soluble, and stable molecule that is easy to produce and deliver. As an angiogenesis inhibitor that specifically targets proliferating endothelial cells, vasostatin has a unique potential for cancer treatment.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Hassanein, M., Bojja, A. S., Glazewski, L., Lu, G., Mason, R.W. (2009). Protein processing by the placental protease, cathepsin P. Mol Hum Reprod 15: 433-442 [Abstract] [Full Text]  
• Racila, E., Link, B. K., Weng, W.-K., Witzig, T. E., Ansell, S., Maurer, M. J., Huang, J., Dahle, C., Halwani, A., Levy, R., Weiner, G. J. (2008). A Polymorphism in the Complement Component C1qA Correlates with Prolonged Response Following Rituximab Therapy of Follicular Lymphoma. Clin. Cancer Res. 14: 6697-6703 [Abstract] [Full Text]  
• Doucet, A., Butler, G. S., Rodriguez, D., Prudova, A., Overall, C. M. (2008). Metadegradomics: Toward in Vivo Quantitative Degradomics of Proteolytic Post-translational Modifications of the Cancer Proteome. Mol. Cell. Proteomics 7: 1925-1951 [Abstract] [Full Text]  
• Butler, G. S., Dean, R. A., Tam, E. M., Overall, C. M. (2008). Pharmacoproteomics of a Metalloproteinase Hydroxamate Inhibitor in Breast Cancer Cells: Dynamics of Membrane Type 1 Matrix Metalloproteinase-Mediated Membrane Protein Shedding. Mol. Cell. Biol. 28: 4896-4914 [Abstract] [Full Text]  
• Cai, K. X., Tse, L. Y., Leung, C., Tam, P. K.H., Xu, R., Sham, M. H. (2008). Suppression of Lung Tumor Growth and Metastasis in Mice by Adeno-Associated Virus-Mediated Expression of Vasostatin. Clin. Cancer Res. 14: 939-949 [Abstract] [Full Text]  
• Kurozumi, K., Hardcastle, J., Thakur, R., Yang, M., Christoforidis, G., Fulci, G., Hochberg, F. H., Weissleder, R., Carson, W., Chiocca, E. A., Kaur, B. (2007). Effect of Tumor Microenvironment Modulation on the Efficacy of Oncolytic Virus Therapy. JNCI J Natl Cancer Inst 99: 1768-1781 [Abstract] [Full Text]  
• Moenner, M., Pluquet, O., Bouchecareilh, M., Chevet, E. (2007). Integrated Endoplasmic Reticulum Stress Responses in Cancer. Cancer Res. 67: 10631-10634 [Abstract] [Full Text]  
• Belloni, D., Scabini, S., Foglieni, C., Veschini, L., Giazzon, A., Colombo, B., Fulgenzi, A., Helle, K. B., Ferrero, M. E., Corti, A., Ferrero, E. (2007). The vasostatin-I fragment of chromogranin A inhibits VEGF-induced endothelial cell proliferation and migration. FASEB J. 21: 3052-3062 [Abstract] [Full Text]  
• Perri, S. R., Martineau, D., Francois, M., Lejeune, L., Bisson, L., Durocher, Y., Galipeau, J. (2007). Plasminogen Kringle 5 blocks tumor progression by antiangiogenic and proinflammatory pathways. Molecular Cancer Therapeutics 6: 441-449 [Abstract] [Full Text]  
• Pal, S., Wu, J., Murray, J. K., Gellman, S. H., Wozniak, M. A., Keely, P. J., Boyer, M. E., Gomez, T. M., Hasso, S. M., Fallon, J. F., Bresnick, E. H. (2006). An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis. JCB 174: 1047-1058 [Abstract] [Full Text]  
• Narazaki, M., Tosato, G. (2006). Tumor cell populations differ in angiogenic activity: a model system for spontaneous angiogenic switch can tell us why.. JNCI J Natl Cancer Inst 98: 294-295 [Full Text]  
• Li, L, Yuan, Y-Z, Lu, J, Xia, L, Zhu, Y, Zhang, Y-P, Qiao, M-M (2006). Treatment of pancreatic carcinoma by adenoviral mediated gene transfer of vasostatin in mice. Gut 55: 259-265 [Abstract] [Full Text]  
• Hong, G. K., Kumar, P., Wang, L., Damania, B., Gulley, M. L., Delecluse, H.-J., Polverini, P. J., Kenney, S. C. (2005). Epstein-Barr Virus Lytic Infection Is Required for Efficient Production of the Angiogenesis Factor Vascular Endothelial Growth Factor in Lymphoblastoid Cell Lines. J. Virol. 79: 13984-13992 [Abstract] [Full Text]  
• Arca, B., Lombardo, F., Valenzuela, J. G., Francischetti, I. M. B., Marinotti, O., Coluzzi, M., Ribeiro, J. M. C. (2005). An updated catalogue of salivary gland transcripts in the adult female mosquito, Anopheles gambiae. J. Exp. Biol. 208: 3971-3986 [Abstract] [Full Text]  
• Wheelock, A. M., Boland, B. C., Isbell, M., Morin, D., Wegesser, T. C., Plopper, C. G., Buckpitt, A. R. (2005). In Vivo Effects of Ozone Exposure on Protein Adduct Formation by 1-Nitronaphthalene in Rat Lung. Am. J. Respir. Cell Mol. Bio. 33: 130-137 [Abstract] [Full Text]  
• Nyberg, P., Xie, L., Kalluri, R. (2005). Endogenous Inhibitors of Angiogenesis. Cancer Res. 65: 3967-3979 [Abstract] [Full Text]  
• Berwin, B., Delneste, Y., Lovingood, R. V., Post, S. R., Pizzo, S. V. (2004). SREC-I, a Type F Scavenger Receptor, Is an Endocytic Receptor for Calreticulin. J. Biol. Chem. 279: 51250-51257 [Abstract] [Full Text]  
• Park, Y. W., Kang, Y. M., Butterfield, J., Detmar, M., Goronzy, J. J., Weyand, C. M. (2004). Thrombospondin 2 Functions as an Endogenous Regulator of Angiogenesis and Inflammation in Rheumatoid Arthritis. Am. J. Pathol. 165: 2087-2098 [Abstract] [Full Text]  
• Vucenik, I., Passaniti, A., Vitolo, M. I., Tantivejkul, K., Eggleton, P., Shamsuddin, A. M. (2004). Anti-angiogenic activity of inositol hexaphosphate (IP6). Carcinogenesis 25: 2115-2123 [Abstract] [Full Text]  
• Bamberger, E S, Perrett, C W (2002). Angiogenesis in epithelian ovarian cancer. Mol. Pathol. 55: 348-359 [Abstract] [Full Text]  
• Goicoechea, S., Pallero, M. A., Eggleton, P., Michalak, M., Murphy-Ullrich, J. E. (2002). The Anti-adhesive Activity of Thrombospondin Is Mediated by the N-terminal Domain of Cell Surface Calreticulin. J. Biol. Chem. 277: 37219-37228 [Abstract] [Full Text]  
• Tanaka, K., Sonoo, H., Kurebayashi, J., Nomura, T., Ohkubo, S., Yamamoto, Y., Yamamoto, S. (2002). Inhibition of Infiltration and Angiogenesis by Thrombospondin-1 in Papillary Thyroid Carcinoma. Clin. Cancer Res. 8: 1125-1131 [Abstract] [Full Text]  
• Streit, M., Stephen, A. E., Hawighorst, T., Matsuda, K., Lange-Asschenfeldt, B., Brown, L. F., Vacanti, J. P., Detmar, M. (2002). Systemic Inhibition of Tumor Growth and Angiogenesis by Thrombospondin-2 Using Cell-based Antiangiogenic Gene Therapy. Cancer Res. 62: 2004-2012 [Abstract] [Full Text]  
• Lange-Asschenfeldt, B., Weninger, W., Velasco, P., Kyriakides, T. R., von Andrian, U. H., Bornstein, P., Detmar, M. (2002). Increased and prolonged inflammation and angiogenesis in delayed-type hypersensitivity reactions elicited in the skin of thrombospondin-2-deficient mice. Blood 99: 538-545 [Abstract] [Full Text]  
• Yao, L., Pike, S. E., Tosato, G. (2002). Laminin binding to the calreticulin fragment vasostatin regulates endothelial cell function. J. Leukoc. Biol. 71: 47-53 [Abstract] [Full Text]  
• Pepper, M. S. (2001). Role of the Matrix Metalloproteinase and Plasminogen Activator-Plasmin Systems in Angiogenesis. Arterioscler. Thromb. Vasc. Bio. 21: 1104-1117 [Abstract] [Full Text]  
• Xu, G., Pan, J., Martin, C., Yeung, S.-C. J. (2001). Angiogenesis Inhibition in the in Vivo Antineoplastic Effect of Manumycin and Paclitaxel against Anaplastic Thyroid Carcinoma. J. Clin. Endocrinol. Metab. 86: 1769-1777 [Abstract] [Full Text]  
• Klasa, R. J., List, A. F., Cheson, B. D. (2001). Rational Approaches to Design of Therapeutics Targeting Molecular Markers. ASH Education Book 2001: 443-462 [Abstract] [Full Text]  
• ZHANG, J.-C., CLAFFEY, K., SAKTHIVEL, R., DARZYNKIEWICZ, Z., SHAW, D. E., LEAL, J., WANG, Y.-C., LU, F.-M., MCCRAE, K. R. (2000). Two-chain high molecular weight kininogen induces endothelial cell apoptosis and inhibits angiogenesis: partial activity within domain 5. FASEB J. 14: 2589-2600 [Abstract] [Full Text]  
• Griffioen, A. W., Molema, G. (2000). Angiogenesis: Potentials for Pharmacologic Intervention in the Treatment of Cancer, Cardiovascular Diseases, and Chronic Inflammation. Pharmacol. Rev. 52: 237-268 [Abstract] [Full Text]  
• Colorado, P. C., Torre, A., Kamphaus, G., Maeshima, Y., Hopfer, H., Takahashi, K., Volk, R., Zamborsky, E. D., Herman, S., Sarkar, P. K., Ericksen, M. B., Dhanabal, M., Simons, M., Post, M., Kufe, D. W., Weichselbaum, R. R., Sukhatme, V. P., Kalluri, R. (2000). Anti-angiogenic Cues from Vascular Basement Membrane Collagen. Cancer Res. 60: 2520-2526 [Abstract] [Full Text]  
• Kerbel, R. S. (2000). Tumor angiogenesis: past, present and the near future. Carcinogenesis 21: 505-515 [Abstract] [Full Text]  
• Patel, J. M., Li, Y. D., Zhang, J., Gelband, C. H., Raizada, M. K., Block, E. R. (1999). Increased expression of calreticulin is linked to ANG IV-mediated activation of lung endothelial NOS. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L794-L801 [Abstract] [Full Text]  
• Corbett, E. F., Michalak, K. M., Oikawa, K., Johnson, S., Campbell, I. D., Eggleton, P., Kay, C., Michalak, M. (2000). The Conformation of Calreticulin Is Influenced by the Endoplasmic Reticulum Luminal Environment. J. Biol. Chem. 275: 27177-27185 [Abstract] [Full Text]  
• Le Naour, F., Hohenkirk, L., Grolleau, A., Misek, D. E., Lescure, P., Geiger, J. D., Hanash, S., Beretta, L. (2001). Profiling Changes in Gene Expression during Differentiation and Maturation of Monocyte-derived Dendritic Cells Using Both Oligonucleotide Microarrays and Proteomics. J. Biol. Chem. 276: 17920-17931 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS