Metabolic phenotypes in triple-negative breast cancer

Sewha Kim, Do Hee Kim, Woo Hee Jung, Ja Seung Koo

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1699-1712
Number of pages14
JournalTumor Biology
Volume34
Issue number3
DOIs
Publication statusPublished - 2013 Jun 1

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Triple Negative Breast Neoplasms
Phenotype
Glycolysis
Neoplasms
Stromal Cells
Claudin-3
Claudin-4
Staining and Labeling
Autophagy
Cadherins
Interleukin-8

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Kim, Sewha ; Kim, Do Hee ; Jung, Woo Hee ; Koo, Ja Seung. / Metabolic phenotypes in triple-negative breast cancer. In: Tumor Biology. 2013 ; Vol. 34, No. 3. pp. 1699-1712.
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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.",
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Metabolic phenotypes in triple-negative breast cancer. / Kim, Sewha; Kim, Do Hee; Jung, Woo Hee; Koo, Ja Seung.

In: Tumor Biology, Vol. 34, No. 3, 01.06.2013, p. 1699-1712.

Research output: Contribution to journalArticle

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