Emerging role of the endothelin axis in ovarian tumor progression

被引:74
|
作者
Bagnato, A [1 ]
Spinella, F [1 ]
Rosanò, L [1 ]
机构
[1] Regina Elena Inst Canc Res, Mol Pathol & Ultrastruct Lab, I-00158 Rome, Italy
关键词
D O I
10.1677/erc.1.01077
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:761 / 772
页数:12
相关论文
共 50 条
  • [11] Ezrin and its emerging role in tumor progression: Response
    Mangino, Martin J.
    Tian, Tao
    Lindell, Susanne L.
    CRYOBIOLOGY, 2013, 66 (02) : 94 - 94
  • [12] Ghrelin and its emerging role in tumor pathogenesis and progression
    Xu, Ji-Liang
    Xia, Rong
    Min, Xi
    Sun, Zi-Huan
    Liu, Chun
    OBESITY RESEARCH & CLINICAL PRACTICE, 2015, 9 (02) : 184 - 185
  • [13] Role of Endothelin Axis in Recruitment of Tumor Associated Macrophages in Pancreatic Cancer
    Gupta, S.
    Rachagani, S.
    Johansson, S. L.
    Kumar, S.
    Batra, S. K.
    Datta, K.
    Jain, M.
    PANCREAS, 2014, 43 (08) : 1362 - 1362
  • [14] Expression of endothelin 1 and endothelin A receptor in ovarian carcinoma: Evidence for an autocrine role in tumor growth
    Bagnato, A
    Salani, D
    Di Castro, V
    Wu-Wong, JR
    Tecce, R
    Nicotra, MR
    Venuti, A
    Natali, PG
    CANCER RESEARCH, 1999, 59 (03) : 720 - 727
  • [15] The Emerging Key Role of Klotho in the Hypothalamus-Pituitary-Ovarian Axis
    Xie, Tingting
    Ye, Wenting
    Liu, Jing
    Zhou, Lili
    Song, Yali
    REPRODUCTIVE SCIENCES, 2021, 28 (02) : 322 - 331
  • [16] Emerging role of exosomes in cancer progression and tumor microenvironment remodeling
    Mahshid Deldar Abad Paskeh
    Maliheh Entezari
    Sepideh Mirzaei
    Amirhossein Zabolian
    Hossein Saleki
    Mohamad Javad Naghdi
    Sina Sabet
    Mohammad Amin Khoshbakht
    Mehrdad Hashemi
    Kiavash Hushmandi
    Gautam Sethi
    Ali Zarrabi
    Alan Prem Kumar
    Shing Cheng Tan
    Marios Papadakis
    Athanasios Alexiou
    Md Asiful Islam
    Ebrahim Mostafavi
    Milad Ashrafizadeh
    Journal of Hematology & Oncology, 15
  • [17] Emerging role of exosomes in cancer progression and tumor microenvironment remodeling
    Paskeh, Mahshid Deldar Abad
    Entezari, Maliheh
    Mirzaei, Sepideh
    Zabolian, Amirhossein
    Saleki, Hossein
    Naghdi, Mohamad Javad
    Sabet, Sina
    Khoshbakht, Mohammad Amin
    Hashemi, Mehrdad
    Hushmandi, Kiavash
    Sethi, Gautam
    Zarrabi, Ali
    Kumar, Alan Prem
    Tan, Shing Cheng
    Papadakis, Marios
    Alexiou, Athanasios
    Islam, Md Asiful
    Mostafavi, Ebrahim
    Ashrafizadeh, Milad
    JOURNAL OF HEMATOLOGY & ONCOLOGY, 2022, 15 (01)
  • [18] Ezrin and its emerging role in tumor progression in systemic malignancies
    Kapoor, Shailendra
    CRYOBIOLOGY, 2013, 66 (02) : 93 - 93
  • [19] CCL25-CCR9 axis role in ovarian cancer progression
    Johnson, Erica
    Johnson-Holiday, Crystal
    Singh, Shailesh
    Singh, Udai
    Partridge, Edward
    Lillard, James
    JOURNAL OF IMMUNOLOGY, 2007, 178
  • [20] The Role of the VEGF-C/VEGFRs Axis in Tumor Progression and Therapy
    Chen, Jui-Chieh
    Chang, Yi-Wen
    Hong, Chih-Chen
    Yu, Yang-Hao
    Su, Jen-Liang
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2013, 14 (01) : 88 - 107