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Metabolic phenotypes in triple-negative breast cancer

Authors
 Sewha Kim  ;  Do Hee Kim  ;  Woo-Hee Jung  ;  Ja Seung Koo 
Citation
 TUMOR BIOLOGY, Vol.34(3) : 1699-1712, 2013 
Journal Title
 TUMOR BIOLOGY 
ISSN
 1010-4283 
Issue Date
2013
MeSH
Adult ; Autophagy ; Biomarkers, Tumor/metabolism* ; Breast Neoplasms/classification* ; Breast Neoplasms/metabolism ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Female ; Fibroblasts/metabolism* ; Fibroblasts/pathology ; Glycolysis* ; Humans ; Immunoenzyme Techniques ; Lymphatic Metastasis ; Middle Aged ; Mitochondria/metabolism* ; Mitochondria/pathology ; Neoplasm Grading ; Neoplasm Staging ; Phenotype ; Prognosis ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Stromal Cells/metabolism* ; Stromal Cells/pathology ; Survival Rate ; Tissue Array Analysis
Keywords
Breast cancer ; Reverse Warburg effect ; Triple negative ; Warburg effect
Abstract
The aim of study was to investigate the metabolism of tumor and stromal cells necessary to determine differential tumor–stroma metabolic interactions according to the molecular subtypes of triple-negative breast cancer (TNBC). Tissues from 132 patients of TNBC were prepared for use as tissue microarrays (TMA). Expression of CK5/6, EGFR, claudin 3, claudin 4, claudin7, E-cadherin, AR, GGT1, STAT1, and interleukin-8 was evaluated by immunohistochemical staining using TMA to classify molecular subtypes of TNBC. In addition, immunohistochemical staining for Glut1, CAIX, BNIP3, MCT4, Beclin-1, LC3A, LC3B, and p62 was performed. According to glycolytic status determined by the immunohistochemical expression of Glut-1 and CAIX in tumor and stroma, the metabolic phenotypes of the TNBCs were defined as follows: Warburg type (tumor: glycolysis, stroma: non-glycolysis), reverse Warburg type (tumor: non-glycolysis, stroma: glycolysis), mixed metabolic type (tumor: glycolysis, stroma: glycolysis), and metabolic null type (tumor: non-glycolysis, stroma: non-glycolysis). TNBCs were classified as follows: 79 Warburg type (59.8 %), 7 reverse Warburg type (5.3 %), 24 mixed metabolic type (18.2 %), and 22 metabolic null type (16.7 %). There was no statistical significance between the metabolic phenotypes and molecular subtypes (P = 0.706). Reverse Warburg type showed the most dysfunctional mitochondrial status for stromal cells, while Warburg type showed the most functional mitochondrial status (P = 0.036). Regarding stromal autophagy status, reverse Warburg type showed the most activated status, while all of the Warburg and metabolic null types showed a non-activated status (P < 0.001). In conclusion, Warburg type was the most common metabolic phenotype in TNBC, while reverse Warburg type was the most unusual. Metabolic phenotypes did not differ among the molecular subtypes of TNBCs.
Full Text
http://link.springer.com/article/10.1007%2Fs13277-013-0707-1
DOI
10.1007/s13277-013-0707-1
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Jung, Woo Hee(정우희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/86958
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