Prognostic Importance of Vitamins A, E and Retinol-binding Protein 4 in Renal Cell Carcinoma Patients

Sobotka, R.; Čapoun, Otakar; Kalousová, Marta; Hanuš, Tomáš; Zima, Tomáš; Koštířová, M.; Soukup, Viktor

doi:10.21873/anticanres.11757

Cited by 11 publications

(9 citation statements)

References 13 publications

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“…For instance, Fei et al reported lower RBP4 serum levels in patients with colon cancer than in healthy individuals [17]; on the other hand, Karunanithi et al and Abola et alhave shown that elevated RBP4 is associated with colon cancer progression and liver metastasis [18,19]. 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].…”

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confidence: 99%

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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confidence: 99%

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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“…A recent study revealed that RBP-4, which links obesity and cancer, is one of the pathogenic mechanisms of cancers, including prostate cancer, that is related to obesity (41), breast cancer (42), pancreatic cancer (43), and more. However, Sobotka et al (44) found that low levels of RBP-4 at the time of renal cellar cancer diagnosis are associated with poorer prognosis after surgery, and Lorkova et al (45) veri ed a decrease in RBP-4 levels in ovarian cancer patient sera by two independent methods.…”

Section: Discussionmentioning

confidence: 99%

Inverse association between fasting blood glucose and occurrence of gallbladder cancer in type 2 diabetes mellitus patients: a case-control study

Sheng

Zhang

Chen

et al. 2022

Preprint

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Purpose To explore the reason for the correlation between diabetes mellitus (DM) and gallbladder cancer (GBC) in an epidemiological setting. Methods We summarized the clinical and laboratory data of 2210 GBC patients within 3524 Chinese patients in our hospital from January 2009 to December 2020. Seventeen influencing factors for GBC, including gender, body mass index (BMI), fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), retinol binding protein (RBP), lipid indexes, and others, were analyzed by unconditional logistic regression analysis in this case-control study. Results On univariate logistic regression, GBC likelihood was significantly and positively correlated with serum triglyceride, low-density lipoprotein cholesterol, FINS, and HOMA-IR; being female; BMI; DM; NAFLD; and GSD, and it was significantly negatively correlated with high-density lipoprotein cholesterol and FBG concentrations in serum and with hypertension. In multivariate analysis, FINS was significantly positively associated with GBC risk, while DM had an insignificant negative association, and FBG levels were also not important. HOMA-IR was a most remarkable independent factor of GBC risk in DM patients. FBG levels showed a significant negative relationship to GBC in DM individuals. Conclusions Our findings revealed that the efficient treatment of insulin-resistance is an important approach for decreasing GBC risk, as opposed to lowering blood sugar alone, especially in DM patients. Interestingly, FBG might have an inverse association with the development of GBC in type 2 DM patients. Exciting, we found initially that a dramatic drop in RBP might be helpful in predicting the occurrence of GBC.

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“…The downregulation of this enzyme is also an adaptation of lipid metabolism in hypoxic cancer cells, which is mediated by HIF-1 [ 38 ]. Regarding retinol-binding protein 4, the low expression of Rbp4 has previously been associated with a poorer prognosis in patients with renal cell [ 41 ] and hepatocellular carcinomas [ 42 ] or breast cancer [ 43 ]. Interestingly, a recent single-cell sequencing study analyzing the differences between right- and left-sided colorectal cancer tissues revealed that the specific presence of a subpopulation of RBP4+ cancer cells in the latter was associated with a higher ratio of pre-exhausted/exhausted T cells and an increased responsiveness to immunotherapy [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma

Pouliquen

Malloci

Boissard

et al. 2022

IJMS

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Curcumin exhibits both immunomodulatory properties and anticarcinogenic effects which have been investigated in different experimental tumor models and cancer types. Its interactions with multiple signaling pathways have been documented through proteomic studies on malignant cells in culture; however, in vivo approaches are scarce. In this study, we used a rat model of highly invasive peritoneal mesothelioma to analyze the residual tumor proteomes of curcumin-treated rats in comparison with untreated tumor-bearing rats (G1) and provide insights into the modifications in the tumor microenvironment/malignant cell crosstalk. The cross-comparing analyses of the histological sections of residual tumors from two groups of rats given curcumin twice on days 21 and 26 after the tumor challenge (G2) or four times on days 7, 9, 11 and 14 (G3), in comparison with G1, identified a common increase in caveolin-1 which linked with significant abundance changes affecting 115 other proteins. The comparison of G3 vs. G2 revealed additional features for 65 main proteins, including an increase in histidine-rich glycoprotein and highly significant abundance changes for 22 other proteins regulating the tumor microenvironment, linked with the presence of numerous activated T cells. These results highlight new features in the multiple actions of curcumin on tumor microenvironment components and cancer cell invasiveness.

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Prognostic Importance of Vitamins A, E and Retinol-binding Protein 4 in Renal Cell Carcinoma Patients

Abstract: Low levels of vitamin A, E and RBP4 at the time of RCC diagnosis are associated with a poorer prognosis after surgery.

Cited by 11 publications

References 13 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

Inverse association between fasting blood glucose and occurrence of gallbladder cancer in type 2 diabetes mellitus patients: a case-control study

Proteomes of Residual Tumors in Curcumin-Treated Rats Reveal Changes in Microenvironment/Malignant Cell Crosstalk in a Highly Invasive Model of Mesothelioma

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