Expression of endothelin 1 and endothelin A receptor in HPV‐associated cervical carcinoma: new potential targets for anticancer therapy

Venuti, Aldo; Salani, Debora; Manni, Vanessa; Poggiali, Federica; Bagnato, Anna

doi:10.1096/fj.00-0024com

Cited by 55 publications

(45 citation statements)

References 21 publications

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“…Some findings [16][17][18][19] suggest that endothelin axis plays an important role in a series of events related to tumor development, including mitogenesis [20,21] and escape from apoptosis [22,23] . Moreover, ET-1 expression has been linked to induction of endothelial cell growth, angiogenesis [24][25][26] and epithelial to mesenchymal transition [27][28][29] , resulting in an increased invasiveness and metastases of some tumors.…”

Section: Discussionmentioning

confidence: 99%

Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B

Jiao

Xu²,

Pan³

et al. 2007

WJG

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Section: Discussionmentioning

confidence: 99%

Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B

Jiao

Xu²,

Pan³

et al. 2007

WJG

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“…In melanoma (18) and lung cancer (33) ET B R also seems to be the predominantly expressed receptor, whereas in other tumour entities, e.g. prostate (19), ovarian (11) and cervical cancer (34), ET A R has been reported to be overexpressed more frequently.…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic relevance of endothelin-B receptor in vulvar cancer

Eltze

Bertolin²,

Korsching³

et al. 2007

Oncol Rep

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Abstract. Overexpression of endothelin (ET)-1 and its receptors, ET A R and ET B R, commonly referred to as the 'ET-axis', has been demonstrated to play a role in cancer progression for various human tumours. Based on these results we propose a similar role of the expression of the ET-axis in vulvar cancer. Expression of the ET-axis was investigated immunohistochemically using tissue microarrays with tumour samples of 68 vulvar cancer patients. Samples were obtained from patients undergoing local excision or radical vulvectomy. ET-1 expression of tumour cells correlated highly significantly with early stages of vulvar cancer (p=0.004), whereas neither ET A R nor ET B R expression showed any association with TNM stages. High staining levels of ET B R in the tumour tissue were significantly related to tumour progression (p=0.01) and early metastases (p=0.09); low ET B R staining intensity correlated with longer relapse-free survival (p=0.019). In patients with ET B R overexpressing low-stage tumours (pT1-2) we observed a significantly reduced overall survival and disease-free survival (p=0.036 and 0.021, respectively). ET A R expression and ET B R expression were significantly correlative (p=0.018). Accordingly, co-expression of both receptors was related to tumour progression (p=0.022) and an increased risk for local recurrence (p=0.005). These results suggest that, in addition to established histological and clinical prognostic factors, analysis of ET-receptor and, in particular, of ET B R expression by means of simple immunohistochemical analysis might improve prediction of the prognosis for patients with vulvar squamous cell carcinoma.

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“…Increased ET A R expression has been reported in a broad range of human cancers, including prostate, (30) ovarian, (12) breast, (31) colon, (32) lung, (33) cervical, (13) renal (34) and thyroid gland. (35) Overexpression of ET A R is generally associated with a more malignant phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…(8) ET-1 induces cell proliferation directly or synergistically with other growth factors that are relevant in cancer progression. Engagement of ET A R by ET-1 triggers activation of tumor proliferation, (9)(10)(11)(12)(13) VEGF-induced angiogenesis, (14,15) invasiveness (16) and inhibition of apoptosis. (17,18) The ET-1-ET A R autocrine pathway has a key role in the development and progression of prostatic, ovarian and cervical cancers.…”

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confidence: 99%

Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma

Qiang

Zeng²,

Feng³

et al. 2006

Cancer Science

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The endothelin A receptor (ET A R) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ET A R expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ET A R represents a new target in NPC treatment, we tested the therapeutic role of ET A R in NPC. N asopharyngeal carcinoma is common in Southern China, with an annual incidence of 15-50 cases per 100 000 people.(1) NPC is distinct from other epithelial malignancies in the head and neck region in that it affects a relatively young population and has a propensity for distant metastases.(2) NPC is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy. However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor.(3) Randomized trials have confirmed that chemotherapy improves the distant metastasis control rate in patients with locoregionally advanced NPC; however, approximately 20% or more of the patients still have distant metastasis develop despite intensive chemotherapy.(4,5) These findings underscore the need to develop novel strategies in the management of patients with advanced NPC.The family of ET, including ET-1, ET-2 and ET-3, are 21-amino acid peptides exerting many biological effects.(6) Two major receptor subtypes belonging to the G protein-coupled family of receptors mediate ET signals: ET A R, which binds ET-1 and ET-2 with high affinity and ET-3 with low affinity; and ET B R, which binds all ET isopeptides with equal affinity.(7) ET-1, which is the most common circulating form of ET, is produced by many epithelial tumors.(8) ET-1 induces cell proliferation directly or synergistically with other growth factors that are relevant in cancer progression. Engagement of ET A R by ET-1 triggers activation of tumor proliferation, (9-13) VEGF-induced angiogenesis, (14,15) invasiveness (16) and inhibition of apoptosis. (17,18) The ET-1-ET A R autocrine pathway has a key role in the development and progression of prostatic, ovarian and cervical cancers.(9) The major relevance of ET A R in tumor development has led to an extensive search of highly selective antagonists. ABT-627 (Atrasentan), one such antagonist, is orally bioavailable and has suitable pharmacokinetic and toxicity profiles for clinical use. (19,20) ABT-627 has been given to cancer patients in phase II trials for prostate cancer and delayed the time to clinical and prostate-specific antigen progression.(21) Two pivotal randomized, double-blind, placebo-controlled, multinational phase III trials are ongoing in patients with hormone-refractory prostate cancer to verify these findings.We reported previously that patients with advanced-stage NPC had elevated plasma big ET-1 levels compared with the levels in healthy control participants; high pretreatment plasma big ET-1 levels are generally associated with post-treatment distant failure.(22) Our pr...

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Expression of endothelin 1 and endothelin A receptor in HPV‐associated cervical carcinoma: new potential targets for anticancer therapy

Cited by 55 publications

References 21 publications

Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B

Effect of endothelin-1 in esophageal squamous cell carcinoma invasion and its correlation with cathepsin B

Expression and prognostic relevance of endothelin-B receptor in vulvar cancer

Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma

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