Comparative Profiling of Triple-Negative Breast Carcinomas Tissue Glycoproteome by Sequential Purification of Glycoproteins and Stable Isotope Labeling

Background/Aims: Previous preclinical and clinical studies have reported a positive correlation between the expression of the C-C chemokine receptor 7 (CCR7) and the incidence of lymph node metastasis in breast cancer. However, the prognostic relevance of CCR7 expression in breast cancer remains contradictory till now. The aim of this study is to assess the correlation of the CCR7 expression with other clinicopathological features and prognosis in breast cancer. Methods: The CCR7 gene amplification and mRNA expression levels from approximately 3,000 patients were retrieved from human breast cancer databases and analyzed. Furthermore, a total of 188 primary triple negative breast cancer patients were enrolled in this study (diagnosed since January 2009 to January 2013 from the Second Hospital of Dalian Medical University). The protein levels of CCR7 were examined by immunohistochemistry using paraffin-embedded tumor tissues. Results: The analysis of gene amplification and mRNA levels showed the expression of CCR7 in breast cancer correlated with better prognosis. When we compared the CCR7 expressions in different subtypes, the basal-like group showed the highest expression of CCR7 and exhibited a better prognosis. Consistently, Kaplan–Meier analysis of 188 triple negative breast cancer patients showed that the prognosis of patients with positive CCR7 expression was significantly better than those with negative expression (HR=0.642, p=0.0275). Additionally, we also observed a positive correlation between lymph node metastasis and the CCR7 expression (p=0.0096). Conclusions: Our results indicated that elevated CCR7 expression as a marker for increased lymph node metastasis, in addition to serve as an independent prognostic indicator for better overall survival in triple negative breast cancer patients.

Section: Discussionmentioning

confidence: 99%

High Expression of CCR7 Predicts Lymph Node Metastasis and Good Prognosis in Triple Negative Breast Cancer

Sun

et al. 2017

“…Chen et al, through hydrazide-based chemistry method combined with liquid chromatography tandem-mass spectrometry (LC-MS/MS), identified 72 unique N-linked glycoproteins that were significantly regulated in triple negative breast cancers, among which is LGALS3BP. LGALS3BP is a highly-glycosylated galectin-3 binding protein whose bio-physiological activity is not yet well defined, but recent findings point to a possible involvement with cancer growth and progression [225]. …”

Section: Hypoxia Alters Cell Location Of Galectins and Interaction Wimentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

“…Glycosylation was with the hydrolytic products (i.e., glucose and fructose) since sucrose was a non-reducing sugar; indeed, glucose was detected after L2/L3 insonation (with levels of 0, 0, 2.1±0.2, and 10.6±5.7 μg/ml in control, L1-, L2-, and L3-treated samples, respectively). Glycosylation impacted on the function of a protein [12, 13]. Ultrasound can accelerate the hydrolysis of sucrose, and enhance the protein-sugar reactions to form conjugates via free –OH, –COOH or –NH 2 in the protein [14, 15].…”

Section: Resultsmentioning

confidence: 99%

Biphasically Modulating the Activity of Carboxypeptidase G2 with Ultrasound

Ma¹,

Zhang²,

Zheng³

et al. 2017

Background/Aims: Carboxypeptidase G2 (CPG2) has been used for cancer prodrug therapy to realize the targeted release of active drugs, but there yet lacks a means to modulate the CPG2 activity. Here ultrasound was used to modulate the CPG2 activity. Methods: The activity of insonated CPG2 was determined, and then underlying biochemical (i.e., monomer, dimer and conformation) and ultrasonic (i.e., heat and cavitation) mechanisms were explored. Results: Ultrasound (1.0 MHz) increased or decreased the enzymatic activity; the activity decreased as zero- or first-order kinetics, depending on the intensity. L1 (10 W/cm² for 200 s) improved the activity via increasing the specific activity. L2 or L3 (20 W/cm² for 1200 or 3000 s) decreased the activity via disassembling the dimer, degrading the monomer, inducing glycosylation, transforming conformation and decreasing the specific activity. An increase or a slight decrease of activity attributable to 10 W/cm² was reversible, but the activity decrease due to 20 W/cm² was irreversible. The enzymatic modulation was realized via cavitation. Conclusion: Ultrasound can biphasically modulate the CPG2 activity, and can be employed in the CPG2-prodrug therapy to adjust the release and moles of active drugs.