Elevated Serum Levels of Retinol-Binding Protein 4 Are Associated with Breast Cancer Risk: A Case-Control Study

Jiao, Congcong; Cui, Lianhua; Ma, Aiguo; Li, Na; Si, Hongzong

doi:10.1371/journal.pone.0167498

Cited by 31 publications

(30 citation statements)

References 60 publications

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“…A similar tendency (in the case of ER) was observed in our studies ( Figure S3H). However, in contrast to the studies of Jiao et al, our results showed significant differences in the plasma levels of RBP4 between patients with metastatic and nonmetastatic tumors [25]. Moreover, our animal studies on two sister cell lines, nonmetastatic 67NR and metastatic 4T1, confirmed significantly higher RBP4 plasma levels in mice bearing metastatic tumors than in mice bearing nonmetastatic tumors.…”

Section: Discussioncontrasting

confidence: 99%

“…Although several studies have presented the analysis of the effect of RBP4 on several types of cancers, only one study has shown such research on patients with breast cancer [25]. In their case-control study, Jiao et al showed that serum RBP4 levels were positively associated with breast cancer risk among patients with lower BMI (<25 kg/m 2 ) and that patients with ER-or PR-negative tumors possessed significantly higher serum levels of RBP4 [25]. A similar tendency (in the case of ER) was observed in our studies ( Figure S3H).…”

Section: Discussionmentioning

confidence: 99%

“…There are also studies showing the importance of this protein in ovarian, renal, hepatocellular, oral squamous cell, and pancreatic cancer patients [20][21][22][23][24]. Such analyses conducted in patients with breast cancer suggested a link between elevated RBP4 and the risk of breast cancer [25]. The proposed mechanisms of RBP4 effects on cancer cells are dependent on the activation of the signaling receptor and transporter of retinol STRA6 by bound RBP4 and further transduction of the JAK2-STAT3 signaling cascade [18].…”

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confidence: 99%

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Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors

Papiernik

Urbaniak

Kłopotowska

et al. 2020

Cancers

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Retinol-binding protein 4 (RBP4) is proposed as an adipokine that links obesity and cancer. We analyzed the role of RBP4 in metastasis of breast cancer in patients and in mice bearing metastatic 4T1 and nonmetastatic 67NR mammary gland cancer. We compared the metastatic and angiogenic potential of these cells transduced with Rbp4 (4T1/RBP4 and 67NR/RBP4 cell lines). Higher plasma levels of RBP4 were observed in breast cancer patients with metastatic tumors than in healthy donors and patients with nonmetastatic cancer. Increased levels of RBP4 were observed in plasma, tumor tissue, liver, and abdominal fat. Moreover, the blood vessel network was highly impaired in mice bearing 4T1 as compared to 67NR tumors. RBP4 transductants showed further impairment of blood flow and increased metastatic potential. Exogenous RBP4 increased lung settlement by 67NR and 4T1 cells. In vitro studies showed increased invasive and clonogenic potential of cancer cells treated with or overexpressing RBP4. This effect is not dependent on STAT3 phosphorylation. RBP4 enhances the metastatic potential of breast cancer tumors through a direct effect on cancer cells and through increased endothelial dysfunction and impairment of blood vessels within the tumor.Cancers 2020, 12, 623 2 of 21 cancer pulmonary metastasis. These processes precede the onset of a phenotypic switch in the lung endothelium toward a mesenchymal phenotype (EndMT), which is parallel to the appearance of the first pulmonary metastatic colonies [7]. Therefore, therapeutic strategies that aim to normalize endothelial dysfunction can decrease the metastatic potential of this type of breast cancer [8][9][10].Apart from its involvement in cancer development, endothelial dysfunction plays an important role in the development of cardiovascular diseases and atherosclerosis. Moreover, in type 2 diabetes mellitus, endothelial dysfunction and insulin resistance often coexist at the earliest stage of atherosclerosis with elevation of serum retinol-binding protein 4 (RBP4), a specific retinol transporter in the blood [11]. It is documented that RBP4 induces inflammation of endothelial cells in vitro. This action is due to the stimulation of proinflammatory molecules involved in leukocyte recruitment and their adherence to endothelium, and it is independent of retinol and the RBP4 membrane receptor STRA6 [12]. Endothelial inflammation induced by RBP4 is largely mediated by toll-like receptor 4 (TLR4), and in part, through the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways [13]. Moreover, in isolated aorta rings, RBP4 treatment significantly increased NO production, stimulating the PI3K/Akt/eNOS pathway [14].RBP4, classified as adipokine [15], is proposed as the protein linking obesity and cancer [16]. Studies have shown various correlations between RBP4 plasma/tumor tissue levels and the development of certain types of cancer. For instance, Fei et al. reported lower RBP4 serum levels in patients with colon cancer than in healthy individu...

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors

Papiernik

Urbaniak

Kłopotowska

et al. 2020

Cancers

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“…The elevated level of RBP 4 is reported previously in breast cancer. 22 In our case, the RBP 4 is also upregulated in smoker, COPD, and lung cancer. We have also noted that there is sequential increase of two proteins including haptoglobulin and alpha-1-antitrypsin from healthy, smoker, COPD to lung cancer.…”

Section: Discussionsupporting

confidence: 48%

A comparative protein analysis of lung cancer, along with three controls using a multidimensional proteomic approach

Saleem

Raza

Musharraf

2019

Exp Biol Med (Maywood)

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Lung cancer is an important respiratory disease accounting for millions of deaths worldwide. Developments in proteomics techniques and mass spectrometry offer comprehensive answers to unravel the complexities of lethal diseases such as lung cancer at the molecular level. The current study focuses on the proteomic profiling of lung cancer and its comparison with other controls including chronic smoker (high-risk individuals), obstructive pulmonary disease (COPD), and healthy control. A multistep proteomic strategy was used on the pooled plasma of each group including depletion of seven most abundant proteins, 2D-SDS-PAGE separation followed by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF-TOF-MS) analysis. Total 23 proteins were identified, and out of them only 7 proteins were found to be expressed in increased amounts in disease and smoker groups as compared to healthy group including haptoglobin, retinol binding protein 4 (RBP 4), alpha-1 antitrypsin, Ig lambda 2 chain C region, Ig alpha-1-chain C region, clusterin, transthyretin (TTR). Haptoglobin and alpha-1-antitrypsin were found to be sequentially increased in healthy control along with smoker, COPD, and lung cancer. The differentially expressed proteins might have a prognostic potential to be used in the progression of COPD to ultimately lung cancer. Impact statement A multistep proteomics fractionation strategy was developed and validated for the discovery of proteomic biomarkers which could be used as potential diagnostic biomarkers for monitoring the progression of disease in smokers and COPD patients towards lung cancer.

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“…We selected 7 SNPs dealing with immune response, metabolic factors, extracellular matrix and inflammatory pathways that have been suggested to be related to tumor development. Secondarily, we evaluated serum retinol levels that have been related to tumor development of different kinds [22,23,[45][46][47] and with the PNPLA3 variant I148M [21,24]. Surprisingly, we did not find any significant association between the majority of the selected SNPs and HCC development, nor between serum retinol levels and PNPLA3 variant I148M.…”

Section: Discussionmentioning

confidence: 79%

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C

Mazzella

Ravaioli

et al. 2019

JGLD

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Background and Aims: Cirrhotic patients with hepatitis C virus (HCV) infection remain at risk of developing hepatocellular carcinoma (HCC) even after the sustained virologic response (SVR). We aimed to evaluate whether the IL28 (rs12979860) single nucleotide polymorphism (SNP) may constitute a predisposing genetic factor and to identify the SVR patients at risk of HCC. Methods: Two hundred patients undergoing DAAs treatment for chronic hepatitis C with advanced fibrosis (F3- F4) were consecutively enrolled. Besides normal routine laboratory testing for HCV, patients’ sera were evaluated also for retinol, retinol-binding protein 4 and the following SNPs: PNPLA3 (rs738409), TM6SF2 (rs58542926), MBOAT7 (rs641738), IL28B (rs12979860), TIMP-1 (rs4898), TIMP-2 (rs8179090), NF-kB promoter (rs28362491). Statistical analyses were conducted using Stata/SE 14.2 statistical software (Stata Corp, College Station, TX). Results: Almost all patients (197/200) obtained SVR24. Seventeen patients had a previous history of treated HCC before DAAs. Six patients developed HCC recurrence and five patients developed de novo HCC after a mean period of 18 months since EOT. All these patients had SVR. A significant association between IL28B – TT genotype and HCC development after DAAs therapy was observed (OR 4.728, CI 95% 1.222 – 18.297, p=0.024). Conclusion: IL28B rs12979860 polymorphism was significantly associated with HCC development after DAAs. Assessment of this SNP may better identify patients at risk of developing HCC after treatment. Further prospective studies are required to confirm these hypotheses.

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Elevated Serum Levels of Retinol-Binding Protein 4 Are Associated with Breast Cancer Risk: A Case-Control Study

Cited by 31 publications

References 60 publications

Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors

Retinol-Binding Protein 4 Accelerates Metastatic Spread and Increases Impairment of Blood Flow in Mouse Mammary Gland Tumors

A comparative protein analysis of lung cancer, along with three controls using a multidimensional proteomic approach

Interleukin 28 Polymorphisms and Hepatocellular Carcinoma Development after Direct Acting Antiviral Therapy for Chronic Hepatitis C

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