Emerging role of the endothelin axis in ovarian tumor progression

Anna Bagnato, Francesca Spinella, Laura Rosanò

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and the ET receptors, ETAR and ETBR, represents a novel target in tumor treatment. ET-1 may directly contribute to tumor growth and indirectly modulate tumor-host interactions in various tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors and melanoma. Extensive experimental evidence links ETAR overexpression with tumor progression in ovarian cancer. ETAR engagement can in fact activate multiple signal transduction pathways including protein kinase C, phosphatidylinositol 3-kinase, mitogen-activated protein kinase and transactivate epidermal growth factor receptor, which play a role in ovarian tumor growth and invasion. The effects of ETAR signaling are wide ranging and involve both cancer cells and their surrounding stroma, including the vasculature. Upon being activated, the ETAR mediates multiple tumor-promoting activities, including enhanced cell proliferation, escape from apoptosis, angiogenesis, epithelial-mesenchymal transition and increased motility and invasiveness. These findings indicate that activation of ETAR by ET-1 is a key mechanism in the cellular signaling network promoting ovarian cancer growth and progression. The predominant role played by ETAR in cancer has led to the development of small molecules that antagonize the binding of ET-1 to ETAR. The emerging preclinical data presented here provide a rationale for the clinical evaluation of these molecules in which targeting the related signaling cascade via ETAR blockade may be advantageous in the treatment of advanced stage ovarian carcinoma.

Original languageEnglish
Pages (from-to)761-772
Number of pages12
JournalEndocrine-Related Cancer
Volume12
Issue number4
DOIs
Publication statusPublished - Dec 2005

Fingerprint

Endothelins
Endothelin-1
Neoplasms
Ovarian Neoplasms
Growth
Endothelin-2
Phosphatidylinositol 3-Kinase
Endothelin Receptors
Epithelial-Mesenchymal Transition
Kaposi's Sarcoma
Mitogen-Activated Protein Kinases
Epidermal Growth Factor Receptor
Brain Neoplasms
Protein Kinase C
Melanoma
Signal Transduction
Cell Proliferation
Apoptosis
Breast Neoplasms
Carcinoma

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism

Cite this

Emerging role of the endothelin axis in ovarian tumor progression. / Bagnato, Anna; Spinella, Francesca; Rosanò, Laura.

In: Endocrine-Related Cancer, Vol. 12, No. 4, 12.2005, p. 761-772.

Research output: Contribution to journalArticle

Bagnato, Anna ; Spinella, Francesca ; Rosanò, Laura. / Emerging role of the endothelin axis in ovarian tumor progression. In: Endocrine-Related Cancer. 2005 ; Vol. 12, No. 4. pp. 761-772.
@article{26ca7e8196634b8f8fc893591eb6756b,
title = "Emerging role of the endothelin axis in ovarian tumor progression",
abstract = "Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and the ET receptors, ETAR and ETBR, represents a novel target in tumor treatment. ET-1 may directly contribute to tumor growth and indirectly modulate tumor-host interactions in various tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors and melanoma. Extensive experimental evidence links ETAR overexpression with tumor progression in ovarian cancer. ETAR engagement can in fact activate multiple signal transduction pathways including protein kinase C, phosphatidylinositol 3-kinase, mitogen-activated protein kinase and transactivate epidermal growth factor receptor, which play a role in ovarian tumor growth and invasion. The effects of ETAR signaling are wide ranging and involve both cancer cells and their surrounding stroma, including the vasculature. Upon being activated, the ETAR mediates multiple tumor-promoting activities, including enhanced cell proliferation, escape from apoptosis, angiogenesis, epithelial-mesenchymal transition and increased motility and invasiveness. These findings indicate that activation of ETAR by ET-1 is a key mechanism in the cellular signaling network promoting ovarian cancer growth and progression. The predominant role played by ETAR in cancer has led to the development of small molecules that antagonize the binding of ET-1 to ETAR. The emerging preclinical data presented here provide a rationale for the clinical evaluation of these molecules in which targeting the related signaling cascade via ETAR blockade may be advantageous in the treatment of advanced stage ovarian carcinoma.",
author = "Anna Bagnato and Francesca Spinella and Laura Rosan{\`o}",
year = "2005",
month = "12",
doi = "10.1677/erc.1.01077",
language = "English",
volume = "12",
pages = "761--772",
journal = "Endocrine-Related Cancer",
issn = "1351-0088",
publisher = "BioScientifica Ltd.",
number = "4",

}

TY - JOUR

T1 - Emerging role of the endothelin axis in ovarian tumor progression

AU - Bagnato, Anna

AU - Spinella, Francesca

AU - Rosanò, Laura

PY - 2005/12

Y1 - 2005/12

N2 - Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and the ET receptors, ETAR and ETBR, represents a novel target in tumor treatment. ET-1 may directly contribute to tumor growth and indirectly modulate tumor-host interactions in various tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors and melanoma. Extensive experimental evidence links ETAR overexpression with tumor progression in ovarian cancer. ETAR engagement can in fact activate multiple signal transduction pathways including protein kinase C, phosphatidylinositol 3-kinase, mitogen-activated protein kinase and transactivate epidermal growth factor receptor, which play a role in ovarian tumor growth and invasion. The effects of ETAR signaling are wide ranging and involve both cancer cells and their surrounding stroma, including the vasculature. Upon being activated, the ETAR mediates multiple tumor-promoting activities, including enhanced cell proliferation, escape from apoptosis, angiogenesis, epithelial-mesenchymal transition and increased motility and invasiveness. These findings indicate that activation of ETAR by ET-1 is a key mechanism in the cellular signaling network promoting ovarian cancer growth and progression. The predominant role played by ETAR in cancer has led to the development of small molecules that antagonize the binding of ET-1 to ETAR. The emerging preclinical data presented here provide a rationale for the clinical evaluation of these molecules in which targeting the related signaling cascade via ETAR blockade may be advantageous in the treatment of advanced stage ovarian carcinoma.

AB - Ovarian cancer is the leading cause of gynecologic cancer-related deaths. The endothelin (ET) axis, which includes ET-1, ET-2, ET-3, and the ET receptors, ETAR and ETBR, represents a novel target in tumor treatment. ET-1 may directly contribute to tumor growth and indirectly modulate tumor-host interactions in various tumors such as prostatic, ovarian, renal, pulmonary, colorectal, cervical, breast carcinoma, Kaposi's sarcoma, brain tumors and melanoma. Extensive experimental evidence links ETAR overexpression with tumor progression in ovarian cancer. ETAR engagement can in fact activate multiple signal transduction pathways including protein kinase C, phosphatidylinositol 3-kinase, mitogen-activated protein kinase and transactivate epidermal growth factor receptor, which play a role in ovarian tumor growth and invasion. The effects of ETAR signaling are wide ranging and involve both cancer cells and their surrounding stroma, including the vasculature. Upon being activated, the ETAR mediates multiple tumor-promoting activities, including enhanced cell proliferation, escape from apoptosis, angiogenesis, epithelial-mesenchymal transition and increased motility and invasiveness. These findings indicate that activation of ETAR by ET-1 is a key mechanism in the cellular signaling network promoting ovarian cancer growth and progression. The predominant role played by ETAR in cancer has led to the development of small molecules that antagonize the binding of ET-1 to ETAR. The emerging preclinical data presented here provide a rationale for the clinical evaluation of these molecules in which targeting the related signaling cascade via ETAR blockade may be advantageous in the treatment of advanced stage ovarian carcinoma.

UR - http://www.scopus.com/inward/record.url?scp=29144470972&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29144470972&partnerID=8YFLogxK

U2 - 10.1677/erc.1.01077

DO - 10.1677/erc.1.01077

M3 - Article

C2 - 16322321

AN - SCOPUS:29144470972

VL - 12

SP - 761

EP - 772

JO - Endocrine-Related Cancer

JF - Endocrine-Related Cancer

SN - 1351-0088

IS - 4

ER -