scholarly journals The Cell Surface Estrogen Receptor, G Protein- Coupled Receptor 30 (GPR30), is Markedly down Regulated during Breast Tumorigenesis

2008 ◽  
Vol 1 ◽  
pp. BCBCR.S557 ◽  
Author(s):  
Indira Poola ◽  
Jessy Abraham ◽  
Aiyi Liu ◽  
Josephine J. Marshalleck ◽  
Robert L. Dewitty

Background GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis. Methods To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα”—positive (n = 54) and ERα”—negative (n = 45) breast cancer tissues to their matched normal tissues. Results We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p < 0.0001 by two sided paired t-test). The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29) who had lymph node metastasis in comparison with tumors from patients (n = 53) who were negative for lymph node metastasis (two sample t-test, p < 0.02), but no association was found with ERα, PR and other tumor characteristics. Conclusions Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.

2021 ◽  
Author(s):  
Haitao Duan ◽  
Yao Huang ◽  
Caihua Zhang ◽  
Juanjuan Cui ◽  
Lianying Guo ◽  
...  

Abstract Background: Atypical chemokine receptors (ACKRs), including DARC, D6 and CCX-CKR, hold very critical roles in cancer invasion and metastasis. The objective of the present study was to determine preliminarily the predictive value of ACKRs in colorectal cancer (CRC). Methods: From 2012 to 2019 in the First Affiliated Hospital of Dalian Medical University, 44 CRC patients were followed up. We performed immunohistochemical analysis, Western blot and RT-PCR analysis on CRC and adjacent normal tissues for investigating the expression of ACKRs and their relationships to clinicopathologic features and survival rate. Results: The expression of three ACKRs, CCX-CKR, DARC and D6, in normal colon tissues is higher than that in colorectal cancer tissues. Meanwhile, the expression of corresponding ligands CCL21, CCL2 and CCL22 shows the opposite. Low expression of ACKRs in colon cancer tissues was closely related to the potential of lymph node metastasis (P= 0.001). When compared with triple-negative ACKR expression, co-expression of the ACKRs predicted better outcomes of colorectal cancer patients with statistical significance (P=0.011). Conclusions: The loss of ACKRs may play important roles in lymph node metastasis of CRC. ACKR expression may be considered as prognostic markers in CRC patients.


2021 ◽  
Author(s):  
Biaoxue Rong ◽  
Hongling Yan ◽  
Ge Wu ◽  
Kai Li ◽  
Min Li ◽  
...  

Abstract Background: Increased Annexin A1 has been showed to be related to malignant biological characteristics of tumors; the aim of this study was to evaluate the relationship between the expression level of Annexin A1 and the disease progression and treatment effect of lung adenocarcinoma (LAC). Methods: The expression level of Annexin A1 in LAC tissues and cells was detected by the methods of immunohistochemistry, Real time-PCR and western blotting. The relationship between the expression of Annexin A1 and the disease progression and treatment effect of LAC was evaluated by descriptive statistics, T test and Chi-square test. Results: The protein expression of Annexin A1 was higher in lung cancer tissues and cells than that in normal tissues and 16 human bronchial epithelial (16HBE) cells (p<0.05). The level of Annexin A1 mRNA was higher in lung cancer tissues than that in normal tissues (p<0.05). The increase of Annexin A1 protein and mRNA was associated with the lymph node metastasis, advanced clinical stage (p<0.05). However, surgical resection and chemotherapy for LAC down-regulated the serum concentration of Annexin A1 in patients (p<0.05).Conclusions: Increased Annexin A1 protein and mRNA in LAC tissues correlate with the poor differentiation, lymph node metastasis and advanced stage of LAC. Surgical resection and chemotherapy for LAC down-regulate the serum concentration of Annexin A1 in patients. The results indicate that expression level of Annexin A1 contributes to the evaluation of the disease progression and treatment effect of LAC.


2015 ◽  
Vol 2015 ◽  
pp. 1-9
Author(s):  
Wenchao Zhang ◽  
Xudong Wang ◽  
Kai Yue ◽  
Su Liu ◽  
Xiaonan Liu

The CXCL12-CXCR4 biological axis consisting of the chemotactic factor CXCL12 and its specific receptor CXCR4 plays an important role in oral cancer metastasis. High expression of CXCR4 may help oral squamous cancer cells invade local tissues and metastasize to lymph nodes. No obvious association was observed between CXCL12 expression and lymph node metastasis, suggesting that CXCL12 chemotaxis may only be related to CXCR4 expression on the tumor cell membrane. KDEL can be retained by receptors on the surface of the intracellular endoplasmic reticulum (ER) and also be called an ER retention signal sequence. So we adopted the KDEL sequence in this study to generate a CXCL12-KDEL fusion protein in combination with a traceable E-tag label. As such, CXCL12 was retained in the ER. Specific receptor CXCR4 binds to the CXCL12-KDEL, was also retained in the ER, and was thus prevented from reaching the oral squamous cancer cell surface. We reduced the cell surface level of CXCR4 and called the technique “intracellular sequestration.” By this way, we have finished blocking of CXCL12-CXCR4 biological axis and inhibiting lymph node metastasis of oral carcinoma.


2018 ◽  
Vol Volume 10 ◽  
pp. 1969-1974 ◽  
Author(s):  
Mahnaz Seifi-Alan ◽  
Roshanak Shams ◽  
Mojgan Bandehpour ◽  
Reza Mirfakhraie ◽  
Soudeh Ghafouri-Fard

2021 ◽  
Author(s):  
Yongzhi Niu ◽  
Wei Wang ◽  
Xiaodan Jiang ◽  
Jisheng Zhang ◽  
Yichuan Huang ◽  
...  

Abstract Human endogenous retrovirus-H long terminal repeat-associating protein 2 (HHLA2) is a newly identified immune checkpoint molecule that was aberrantly expressed in many malignant tumors. However, its expression in medullary thyroid carcinoma (MTC) is still unclear. This study aimed to investigate the HHLA2 expression in MTC tissues and to evaluate the relationships between its expression and clinicopathologic together with prognostic relevance. Using 51 surgical specimens obtained from MTC patients, the expression levels of the HHLA2 protein in MTC tumor tissues and adjacent noncancerous tissues were measured by immunohistochemistry, and its correlations with clinicopathologic and prognostic features were analyzed. Status of CD8+ tumor-infiltrating lymphocytes (TILs) was also investigated. The results showed that HHLA2 was only detected in tumor tissues, and that 31.4% of the MTC patients had high expression of HHLA2. High HHLA2 expression was significantly associated with lymph node metastasis and advanced AJCC stages (P=0.005). There existed an inverse trend between HHLA2 expression and CD8+ TILs infiltration in MTC tumor samples (P=0.042). The log-rank test showed a shorter disease-free survival in patients with high HHLA2 expression (P=0.002). The disease-free survival rates were also significantly low in cases of MTC with lymph node metastasis, AJCC stages III-IV and multifocality. Multivariate Cox analysis confirmed that HHLA2 acted as an independent predictive factor in the disease-free survival of MTC patients (HR=4.138, 95%CI: 1.027-16.667, P=0.046). Taken together, HHLA2 is highly expressed in MTC patients, and is a poor prognostic biomarker of disease-free survival of MTC patients.


2021 ◽  
Author(s):  
Jiayou Liu ◽  
Shaoli Xie ◽  
Linglong Mo ◽  
Lulan Pu ◽  
Mingfei Xu ◽  
...  

Abstract Background Genetic mutations have been reported in many tumors. In this study, we aimed to examine whether ANXA2 mutations occur in breast cancer and to investigate their association with clinicopathological characteristics in patients. Materials and Methods We collected breast cancer and adjacent normal tissue samples from 112 patients, extracted total RNA, and performed PCR-SSCP and bidirectional Sanger sequencing. ANXA2 mutations were identified by NCBI BLAST (blastn and blastx), and their correlation with clinical data were analyzed. Results ANXA2 mutations were detected in breast cancer tissues (missense mutations 38.39%) at a higher incidence than in adjacent normal tissues (missense mutations 8.04%) and mainly located in domain and repeats 1. Moreover, mutations in breast cancer tissues were associated with clinical stages, molecular subtype, ER, PR, and lymph-node metastasis of patients. Within a mean follow-up time of 52.5 months, the 5-year OS of patients with missense mutations was lower than those without. Among those mutations, c.(350AG > GA), c.(375G > A), c.(487T > A) and c.(693G > A) were associated with younger patients. c.(350AG > GA) was related to higher clinical stage and lymph-node metastasis. c.(375G > A) was linked to HER2(-) cases, while c.(693G > A) tended to be TNBC cases. Conclusion ANXA2 missense mutations mainly occurred on domain and repeats 1 in breast cancer, which may be associated with pathogenesis, clinical stage, molecular subtyping, lymph node metastasis and 5-year OS of breast cancer. These mutations may contribute to the early screening, diagnosis, and targeted treatment of breast cancer.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yang Peng ◽  
Hong Hong Wang

Abstract Circular RNAs (circRNAs) are differentially expressed in various tumours, but the expression and regulatory mechanisms of circular RNA ITCH (cir-ITCH) in gastric cancer remain unclear. For this reason, in the present study, we assessed the expression of cir-ITCH and the associated regulatory mechanism of cir-ITCH in gastric cancer. Through RTq-PCR assays, we observed that cir-ITCH expression was attenuated in gastric cancer cell lines and tissues, with cir-ITCH expression in gastric cancer tissues with lymph node metastasis being considerably lower than that observed in gastric cancer tissues without lymph node metastasis. In addition, we demonstrated that cir-ITCH or linear ITCH may be a useful marker for gastric cancer prognosis by Kaplan–Meier survival analysis. We also showed that cir-ITCH overexpression could increase linear ITCH expression through miR-17 via RNA immunoprecipitation (RIP) and luciferase reporter assays. Moreover, in vivo and in vitro experimental results showed that cir-ITCH can act as a tumour suppressor to prevent gastric cancer tumourgenesis by sponging miR-17. The Wnt/β-catenin pathway plays a crucial role during the carcinogenesis of cancers, and we observed that cir-ITCH could negatively regulate Wnt/β-catenin signalling, which could be restored by miR-17. In summary, cir-ITCH was shown to prevent gastric cancer tumourgenesis through the Wnt/β-catenin signalling pathway by sequestering miR-17.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16554-e16554
Author(s):  
Yicheng Zhou ◽  
Honglei Zhu ◽  
Xuezhou Pang ◽  
Yang Shen ◽  
Yu He ◽  
...  

e16554 Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and has a very high morbidity and mortality rate. The IL-6/STAT3 axis can simultaneously promote the expansion of immunosuppressive cells.This study detected IL-6, STAT3 and PD-L1 in ESCC and analyzed the potential clinical application value. Methods: Between July 2018 and April 2019, 70 ESCC patients underwent radical thoracic surgery at Affiliated Hospital of North Sichuan Medical College. RT-PCR was used to detect PD-L1, IL-6, and STAT3 mRNA expression in cancer and adjacent normal tissues. Western blot detection of PD-L1, IL-6, and STAT3 was performed in 40 cancer and adjacent normal tissues. The correlation of PD-L1, IL-6 and STAT3 protein expression with tumor invasion depth, tumor size, lymph node metastasis,clinical stage and other clinicopathological characteristics as well as the correlation between the three proteins were analyzed statistically. Results: The mRNA levels of PD-L1, IL-6, and STAT3 in 70 ESCC patients were significantly different between cancerous and adjacent normal tissues (P < 0.001). In 40 ESCC patients, 28 ESCC tissues showed significantly higher PD-L1 expression than adjacent normal tissue (28/12, P < 0.001), 29 ESCC tissues showed significantly higher STAT3 expression (29/11,P = 0.009 ), and 27 ESCC tissues showed significantly higher IL-6 expression (27/13,P = 0.042). There was no correlation between PD-L1 expression and age, sex, tumor site or maximum tumor diameter, but PD-L1 expression showed a positive correlation with T stage (P = 0.009), lymph node metastasis (P = 0.044), and clinical stage (P = 0.033). There was no correlation between STAT3 expression and age, sex, tumor site, maximum tumor diameter, lymph node metastasis or clinical stage, but STAT3 expression showed a positive correlation with T stage (P = 0.025). IL-6 expression was not correlated with age, sex, maximum tumor diameter, lymph node metastasis or clinical stage, but IL-6 expression showed a positive correlation with T stage ( P = 0.003)and tumor site (P = 0.011). In addition, PD-L1 expression showed a positive correlation with STAT3 (P = 0.013) and IL-6 ( P = 0.008), and STAT3 showed a positive correlation with IL-6 ( P = 0.027). Conclusions: PD-L1, IL-6, and STAT3 are highly expressed in ESCC and their protein levels exhibit a positive correlation. The IL-6/STAT3 signaling pathway proteins may be a potential biomarker predicting the efficacy of immunotherapy by affecting the expression of PD-L1.


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