Abstract 2287
Background
Triple-negative breast cancer (TNBC) is account for 10∼25% of breast cancer incidence with more aggressive phenotype, metastatic capability, and poorer prognosis than other subtypes. Altered cancer metabolism is an emerging hallmark of cancer. Previous studies reported that TNBC cells exhibit greater aerobic glycolysis than non-TNBC cells; however, the detailed regulatory mechanism is largely unknown.
Methods
The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze expression of glycolytic genes and clinical relevance in TNBC patients. Immunohistochemistry assay was performed to confirm the expression of glycolytic gene in breast cancer tissues. Gain-of-function and loss-of-function studies were conducted in TNBC cell lines. The effect of inflammatory microenvironment was carried out by coculture of macrophages and TNBC cells, and the expression of inflammatory cytokines were performed by real-time PCR.
Results
We compared the differential genes expression in TNBC and non-TNBC by in silico analysis. Interestingly, the expression of glucose transporter 3 (Glut3) is upregulated in TNBC patients, compared to non-TNBC patients. Mechanistically, overexpression of Glut3 regulated the expression of epithelial-mesenchymal transition (EMT) genes and promoted invasiveness and metastasis of TNBC cells. Activation of IL6/STAT3 signaling regulates the expression of Glut3 and glycolytic genes, and coexpression of IL6/Glut3 rendered poorer survival outcome, particularly in TNBC. Moreover, conditioned medium (CM) from Glut3-expressing tumor cells induced macrophage activation and production of pro-inflammatory cytokines, and patients with high Glut3 level associated with inflammaotry signautres.
Conclusions
Upregulation of IL6/STAT3 signaling axis promotes expression of Glut3 and glycolytic genes. Elevation of Glut3 in TNBC induces macrophage activation and production of pro-inflammatory cytokines. Our data show the possible association between glucose metabolism and inflammatory microenvironment in TNBC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The author.
Funding
Ministry of Science and Technology, Taiwan.
Disclosure
The author has declared no conflicts of interest.
Resources from the same session
5103 - CANOPY phase 3 program: Three studies evaluating canakinumab in patients with non-small cell lung cancer (NSCLC)
Presenter: Luis Paz-Ares
Session: Poster Display session 1
Resources:
Abstract
3666 - The Elderly Patient Individualized Chemotherapy (EPIC) trial, a study for an aged population of non-small cell lung cancer.
Presenter: Francesco Passiglia
Session: Poster Display session 1
Resources:
Abstract
4799 - KEYNOTE-495/KeyImPaCT: A Randomized, Biomarker-Directed, Phase 2 Trial of Pembrolizumab-Based Therapy for Non–Small Cell Lung Cancer (NSCLC)
Presenter: Martin Gutierrez
Session: Poster Display session 1
Resources:
Abstract
6035 - Safety, tolerability and activity of autologous T cells with enhanced T-cell receptors specific to NY ESO 1/LAGE 1a (GSK3377794) alone, or in combination with pembrolizumab, in advanced non small cell lung cancer: A Phase 1b/2a randomised pilot study
Presenter: Karen Reckamp
Session: Poster Display session 1
Resources:
Abstract
2176 - IFCT-1701 DICIPLE: a randomized phase 3 trial comparing continuation Nivolumab-Ipilimumab doublet immunotherapy until progression versus observation in patients with PDL1-positive stage IV Non-Small Cell Lung Cancer (NSCLC) after Nivolumab-Ipilimumab induction treatment
Presenter: Gerard Zalcman
Session: Poster Display session 1
Resources:
Abstract
2352 - ATALANTE-1 randomized phase 3 trial, OSE-2101 versus standard treatment as second or third line in HLA-A2 positive advanced non-small cell lung cancer (NSCLC) patients
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
2451 - Phase Ib dose-escalation/expansion study of BI 836880, a VEGF/Ang2-blocking nanobody®, in combination with BI 754091, an anti-PD-1 antibody, in patients with advanced solid tumours
Presenter: Nicolas Girard
Session: Poster Display session 1
Resources:
Abstract
4285 - Radiosurgery followed by Tumor Treating Fields (TTFields) for brain metastases (1-10) from NSCLC in the phase 3 METIS trial
Presenter: Minesh Mehta
Session: Poster Display session 1
Resources:
Abstract
4909 - Nivolumab plus ipilimumab (NI) versus chemotherapy plus nivolumab (CN) in squamous cell lung cancer (SqCLC): the SQUINT trial
Presenter: Lorenza Landi
Session: Poster Display session 1
Resources:
Abstract
4125 - DUBLIN-3, a Stage IIIb/IV NSCLC Phase (Ph)3 Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone
Presenter: Ramon Mohanlal
Session: Poster Display session 1
Resources:
Abstract