The Relationship between Urotensin II and its Receptor and the Clinicopathological Parameters of Breast Cancer

Abstract

BackgroundUrotensin II is a vasoactive polypeptide. It is known that some vasoactive polypeptides are produced and secreted by tumor cells, and act as a paracrine growth stimulant. The aim of this study was to examine the relationship between urotensin II and its receptor’s messenger RNA expression in breast cancer.Material/MethodsFifty-nine women with breast cancer were included in this study. The median age was 48 years. The relationships between urotensin II and urotensin II receptor mRNA expressions, which were derived from fresh breast cancer tissues and adjacent normal breast tissues, and clinical and pathological parameters, were assessed.ResultsWe found expressions of urotensin II mRNA and its receptor in 55 of 59 breast cancer tissues and in 55 of 59 normal breast tissues. We found a positive significant correlation between urotensin II and its receptor (p=0.001, r=0.632), and found a negative, but insignificant, correlation between urotensin II and age (p=0.038, r=−0.281). Urotensin II levels were higher in the premenopausal group compared to the postmenopausal group (p<0.05). The mean urotensin II receptor expression was higher in the premenopausal group (p<0.05) compared to the postmenopausal group, and its expression was also higher in the group without extra-nodal invasion compared to that of the group with extra-nodal invasion (p=0.001). Urotensin II levels were higher in the group without lymphatic invasion compared to the group with lymphatic invasion (p=0.048).ConclusionsThis study is the first in the English medical literature to determine the urotensin II and its receptor mRNA expressions in breast cancer tissues. Consequently, urotensin II seems be associated with menopausal status, and extra-nodal and lymphatic invasion.

Development of Novel 111-In-Labelled DOTA Urotensin II Analogues for Targeting the UT Receptor Overexpressed in Solid Tumours

“…Furthermore, hUII was able to increase the proliferation rate of both tumour cell lines only observable after 48 h period incubation, at low and high hUII concentrations ( Figure 5C). These data are in a good agreement with studies showing that UT and/or UII are over-expressed in a wide variety of solid tumours [41][42][43][44]58] and participate in tumorigenic mechanisms such as cell migration and/or proliferation. These data have been reported for cancers of prostate [59], colon [44], liver [79] and lung [48] cancers.…”

“…The neuropeptide UII also participates in critical tumorigenic mechanisms, such as cell migration and/or proliferation [36,46,56] and tumour angiogenesis [57]. The urotensinergic receptor UT is present at the plasma membrane of tumoral cells from lung [42], breast [41], colon [58] or prostate cancer [59]. It has long been accepted that the internalisation of an agonist ligand-receptor complex justifies their use in diagnosing cancer, likely because of the accumulation of radioligand in the tumour cells [60,61].…”

“…High-density UT has been reported in various tumour cell lines [40,41] as well as in human tumour extracts from lung [42], liver [43] and colon [44]. It has also been demonstrated that UII, at very low concentrations, stimulates cell proliferation and/or cell migration from human tumours, e.g., lung [45], colon [44], adrenal [40] cancers or high-grade gliomas [46,47].…”

Urotensin II receptor as a potential biomarker for the prognosis of hepatocellular carcinoma patients

“…As a powerful vasoactive peptide in mammals, initially UII/UTR is reported to play an important role in portal hypertension, renal disease and heart failure ( 5 ). Recent studies demonstrated that UII/UTR may involve in tumorigenesis and tumor progression in many malignant tumors ( 6 ), such as adrenal gland neoplasms ( 7 ), breast carcinoma ( 8 ), pulmonary adenocarcinoma ( 9 ), renal cell carcinoma and colon carcinoma ( 10 ). Our previous study demonstrated that UII and UTR are up-regulated in rat HCC model and human HCC tissue, exogenous UII can increase hepatic oval cell and HCC cell proliferation in vitro ( 11 – 13 ).…”

Urotensin II: an inflammatory cytokine

“…(4) Insulin resistance: plasma levels of UII increase in diabetic patients (Totsune et al 2003) and high levels of UII can induce insulin resistance ) and inhibit glucose uptake in skeletal muscles ). (5) Carcinogenic effects: the expression of UII/UT is correlated with tumor progression, metastasis and prognosis (Wu et al 2010, Balakan et al 2014. UII mediates PKC-and ERK1/2dependent pro-mitogenic signaling pathways (Wang et al 2011) and induces cell transformation to malignant tumor phenotypes (Goldberg et al 2016).…”