© 2005 Oxford University Press
ARTICLE |
Role of Human Cripto-1 in Tumor Angiogenesis
Affiliations of authors: Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory (CB, LS, CC, YS, NK, MH, BW-J), Molecular and Cellular Endocrinology Section, Mammary Biology and Tumorigenesis Laboratory (EG, BKV), Extracellular Matrix Section, Laboratory of Pathology (LG, RS, WGS-S), Experimental Transplantation and Immunology Branch (GT), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Department of Gynecology, Charite Campus Benjamin Franklin, Berlin, Germany (AE); Department of Molecular and Cellular Biology, University of Michigan, Ann Arbor, MI (AR); Division of Haematological Oncology and Department of Experimental Oncology, ITN-Fondazione Pascale, Naples, Italy (NN); Upper Austrian Research GmbH Zentrum, Linz, Austria (CW); Biogen-Idec Inc., Cambridge, MA (MS)
Correspondence to: David S. Salomon, PhD, Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bldg. 10, Rm. 5B39, Bethesda, MD 20892 (e-mail: salomond{at}mail.nih.gov)
Background: Human cripto-1 (CR-1) promotes cell transformation and increases migration and invasion of various mouse and human epithelial cell lines. We investigated whether CR-1 also stimulates angiogenesis. Methods: We used human umbilical vein endothelial cells (HUVECs) to measure in vitro migration with fibronectin-coated Boyden chambers, invasion with Matrigel-coated Boyden chambers, proliferation with a tetrazolium salt, and differentiation with an in vitro Matrigel assay. We investigated new blood vessel formation in vivo by use of Matrigel-filled silicone cylinders implanted under the skin of nude mice and by use of a breast cancer xenograft model with CR-1-transfected or control Neo-transfected MCF-7 human breast cancer cells. We also used a blocking anti-CR-1 monoclonal antibody to investigate the role of CR-1 in angiogenesis in vivo and in vitro. All statistical tests were two-sided. Results: CR-1 stimulated HUVEC proliferation, migration, and invasion and induced HUVEC differentiation into vascular-like structures on Matrigel. In vivo, recombinant CR-1 protein induced microvessel formation in Matrigel-filled silicone cylinders, and microvessel formation was statistically significantly inhibited with a blocking anti-CR-1 monoclonal antibody (CR-1 and antibody = 127% of microvessel formation compared with that in untreated control cylinders and CR-1 alone = 259%; difference = 132%, 95% confidence interval [CI] = 123% to 140%; P<.001). Tumors formed by CR-1-transfected MCF-7 cells in the cleared mammary fat pad of nude mice had higher microvessel density than tumors formed by control Neo-transfected MCF-7 cells (CR-1-transfected cells = 4.66 vessels per field and Neo-transfected cells = 2.33 vessels per field; difference = 2.33 vessels per field, 95% CI = 1.2 to 2.8; P = .004). Conclusion: CR-1 appears to have an important role in the multistep process of angiogenesis.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Bianco, C. Cotten, E. Lonardo, L. Strizzi, C. Baraty, M. Mancino, M. Gonzales, K. Watanabe, T. Nagaoka, C. Berry, et al. Cripto-1 Is Required for Hypoxia to Induce Cardiac Differentiation of Mouse Embryonic Stem Cells Am. J. Pathol., November 1, 2009; 175(5): 2146 - 2158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D'Aniello, E. Lonardo, S. Iaconis, O. Guardiola, A. M. Liguoro, G. L. Liguori, M. Autiero, P. Carmeliet, and G. Minchiotti G Protein-Coupled Receptor APJ and Its Ligand Apelin Act Downstream of Cripto to Specify Embryonic Stem Cells Toward the Cardiac Lineage Through Extracellular Signal-Regulated Kinase/p70S6 Kinase Signaling Pathway Circ. Res., July 31, 2009; 105(3): 231 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Bianco, L. Strizzi, M. Mancino, K. Watanabe, M. Gonzales, S. Hamada, A. Raafat, L. Sahlah, C. Chang, F. Sotgia, et al. Regulation of Cripto-1 Signaling and Biological Activity by Caveolin-1 in Mammary Epithelial Cells Am. J. Pathol., February 1, 2008; 172(2): 345 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Watanabe, C. Bianco, L. Strizzi, S. Hamada, M. Mancino, V. Bailly, W. Mo, D. Wen, K. Miatkowski, M. Gonzales, et al. Growth Factor Induction of Cripto-1 Shedding by Glycosylphosphatidylinositol-Phospholipase D and Enhancement of Endothelial Cell Migration J. Biol. Chem., October 26, 2007; 282(43): 31643 - 31655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hentschke, I. Kurth, U. Borgmeyer, and C. A. Hubner Germ Cell Nuclear Factor Is a Repressor of CRIPTO-1 and CRIPTO-3 J. Biol. Chem., November 3, 2006; 281(44): 33497 - 33504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Bianco, L. Strizzi, M. Mancino, A. Rehman, S. Hamada, K. Watanabe, A. De Luca, B. Jones, G. Balogh, J. Russo, et al. Identification of Cripto-1 as a Novel Serologic Marker for Breast and Colon Cancer Clin. Cancer Res., September 1, 2006; 12(17): 5158 - 5164. [Abstract] [Full Text] [PDF]
|
|