Cancer Research Audrey Hepburn Sign up for Cancer Research eTOC's
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bagnato, A.
Right arrow Articles by Natali, P. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bagnato, A.
Right arrow Articles by Natali, P. G.
[Cancer Research 64, 1436-1443, February 15, 2004]
© 2004 American Association for Cancer Research

Regular Articles

Endothelin B Receptor Blockade Inhibits Dynamics of Cell Interactions and Communications in Melanoma Cell Progression

Anna Bagnato1, Laura Rosanò1, Francesca Spinella1, Valeriana Di Castro1, Raffaele Tecce1 and Pier Giorgio Natali2

1 Laboratories of Molecular Pathology and Ultrastructure and 2 Immunology, Regina Elena Cancer Institute, Rome, Italy

Phenotypic and genotypic analyses of cutaneous melanoma have identified the endothelin B receptor (ETBR) as tumor progression marker, thus representing a potential therapeutic target. Here, we demonstrate that activation of ETBR by endothelin-1 (ET-1) and ET-3 leads to loss of expression of the cell adhesion molecule E-cadherin and associated catenin proteins and gain of N-cadherin expression. Exposure of melanoma cells to ET-1 leads to a 60% inhibition in intercellular communication by inducing phosphorylation of gap junctional protein connexin 43. Additionally, activation of the ETBR pathway increases {alpha}vß3 and {alpha}2ß1 integrin expression and matrix metalloproteinase (MMP)-2 and MMP-9, membrane type-1-MMP activation, and tissue inhibitor MMP-2 secretion. The ETBR pathway results into the downstream activation of focal adhesion kinase and extracellular signal-regulated kinase 1/2 signaling pathways, which lead to enhanced cell proliferation, adhesion, migration, and MMP-dependent invasion. The small molecule A-192621, an orally bioavailable nonpeptide ETBR antagonist, significantly inhibits melanoma growth in nude mice. These findings demonstrate that ET-1 and ET-3 through ETBR activation trigger signaling pathways involved in events associated with disruption of normal host-tumor interactions and progression of cutaneous melanoma. Pharmacological interruption of ETBR signaling may represent a novel therapeutic strategy in the treatment of this malignancy.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
M.-N. Raymond, P. Robin, F. De Zen, G. Vilain, and Z. Tanfin
Differential Endothelin Receptor Expression and Function in Rat Myometrial Cells and Leiomyoma ELT3 Cells
Endocrinology, October 1, 2009; 150(10): 4766 - 4776.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
N. R. Druckenbrod and M. L. Epstein
Age-dependent changes in the gut environment restrict the invasion of the hindgut by enteric neural progenitors
Development, September 15, 2009; 136(18): 3195 - 3203.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. Binder, T. Hagemann, S. Sperling, M. Schulz, T. Pukrop, M. J. Grimshaw, and H. Ehrenreich
Stromal endothelin B receptor-deficiency inhibits breast cancer growth and metastasis
Mol. Cancer Ther., August 1, 2009; 8(8): 2452 - 2460.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
L. E. Kandalaft, A. Facciabene, R. J. Buckanovich, and G. Coukos
Endothelin B Receptor, a New Target in Cancer Immune Therapy
Clin. Cancer Res., July 15, 2009; 15(14): 4521 - 4528.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
A. Sekulic, P. Haluska Jr, A. J. Miller, J. G. De Lamo, S. Ejadi, J. S. Pulido, D. R. Salomao, E. C. Thorland, R. G. Vile, D. L. Swanson, et al.
Malignant Melanoma in the 21st Century: The Emerging Molecular Landscape
Mayo Clin. Proc., July 1, 2008; 83(7): 825 - 846.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
M J Grimshaw
Endothelins and hypoxia-inducible factor in cancer
Endocr. Relat. Cancer, June 1, 2007; 14(2): 233 - 244.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
F. Spinella, L. Rosano, V. Di Castro, S. Decandia, M. R. Nicotra, P. G. Natali, and A. Bagnato
Endothelin-1 and Endothelin-3 Promote Invasive Behavior via Hypoxia-Inducible Factor-1{alpha} in Human Melanoma Cells
Cancer Res., February 15, 2007; 67(4): 1725 - 1734.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
C. Van Sant, G. Wang, M. G. Anderson, O. J. Trask, R. Lesniewski, and D. Semizarov
Endothelin signaling in osteoblasts: global genome view and implication of the calcineurin/NFAT pathway
Mol. Cancer Ther., January 1, 2007; 6(1): 253 - 261.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
G. Robert, C. Gaggioli, O. Bailet, C. Chavey, P. Abbe, E. Aberdam, E. Sabatie, A. Cano, A. Garcia de Herreros, R. Ballotti, et al.
SPARC Represses E-Cadherin and Induces Mesenchymal Transition during Melanoma Development.
Cancer Res., August 1, 2006; 66(15): 7516 - 7523.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W. Yan and R. Shao
Transduction of a Mesenchyme-specific Gene Periostin into 293T Cells Induces Cell Invasive Activity through Epithelial-Mesenchymal Transformation
J. Biol. Chem., July 14, 2006; 281(28): 19700 - 19708.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
Y. Berger, C. C. Bernasconi, and L. Juillerat-Jeanneret
Targeting the endothelin axis in human melanoma: combination of endothelin receptor antagonism and alkylating agents.
Experimental Biology and Medicine, June 1, 2006; 231(6): 1111 - 1119.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
L. Rosano, F. Spinella, V. Di Castro, S. Decandia, M. R. Nicotra, P. G. Natali, and A. Bagnato
Endothelin-1 Is Required During Epithelial to Mesenchymal Transition in Ovarian Cancer Progression.
Experimental Biology and Medicine, June 1, 2006; 231(6): 1128 - 1131.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. A. Breau, T. Pietri, O. Eder, M. Blanche, C. Brakebusch, R. Fassler, J. P. Thiery, and S. Dufour
Lack of {beta}1 integrins in enteric neural crest cells leads to a Hirschsprung-like phenotype
Development, May 1, 2006; 133(9): 1725 - 1734.
[Abstract] [Full Text] [PDF]

Home page
 Neuro Oncol DukeHome page
K. S. Aboody, J. Najbauer, N. O. Schmidt, W. Yang, J. K. Wu, Y. Zhuge, W. Przylecki, R. Carroll, P. M. Black, and G. Perides
Targeting of melanoma brain metastases using engineered neural stem/progenitor cells
Neuro-oncol, April 1, 2006; 8(2): 119 - 126.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Lahav, M.-L. Suva, D. Rimoldi, P. H. Patterson, and I. Stamenkovic
Endothelin Receptor B Inhibition Triggers Apoptosis and Enhances Angiogenesis in Melanomas
Cancer Res., December 15, 2004; 64(24): 8945 - 8953.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2004 by the American Association for Cancer Research.