Mitochondrial and glycolytic metabolic compartmentalization in diffuse large B-cell lymphoma

被引：39

作者：

Gooptu, Mahasweta ^{[1
]}

Whitaker-Menezes, Diana ^{[2
]}

Sprandio, John ^{[3
]}

Domingo-Vidal, Marina ^{[2
]}

Lin, Zhao ^{[2
]}

Uppal, Guldeep ^{[4
]}

Gong, Jerald ^{[4
]}

Fratamico, Roberto ^{[2
]}

Leiby, Benjamin ^{[5
]}

Dulau-Florea, Alina ^{[6
]}

Caro, Jaime ^{[7
]}

Martinez-Outschoorn, Ubaldo ^{[2
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA

[2] Thomas Jefferson Univ, Dept Med Oncol, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[3] Consultants Med Oncol & Hematol, Broomall, PA USA

[4] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA

[5] Thomas Jefferson Univ, Div Biostat, Dept Clin Pharmacol, Philadelphia, PA 19107 USA

[6] NIH, Dept Lab Med, Hematol, Bldg 10, Bethesda, MD 20892 USA

[7] Thomas Jefferson Univ, Dept Med, Cardeza Fdn Hematol Res, Philadelphia, PA 19107 USA

来源：

SEMINARS IN ONCOLOGY | 2017年 / 44卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Monocarboxylate Transporter; Oxidative Phosphorylation; Glycolysis; Tumor-Microenvironment; ASCITES TUMOR-CELLS; RECEPTOR TOM20; CANCER-CELLS; SUCCINATE-DEHYDROGENASE; PROTEIN IMPORT; FDG PET/CT; MCT1; EXPRESSION; HYPOXIA; GLUCOSE;

D O I：

10.1053/j.seminoncol.2017.10.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Metabolic heterogeneity between neoplastic cells and surrounding stroma has been described in several epithelial malignancies; however, the metabolic phenotypes of neoplastic lymphocytes and neighboring stroma in diffuse large B-cell lymphoma (DLBCL) is unknown. We investigated the metabolic phenotypes of human DLBCL tumors by using immunohistochemical markers of glycolytic and mitochondrial oxidative phosphorylation (OXPHOS) metabolism. The lactate importer MCT4 is a marker of glycolysis, whereas the lactate importer MCT1 and TOMM20 are markers of OXPHOS metabolism. Staining patterns were assessed in 33 DLBCL samples as well as 18 control samples (non-neoplastic lymph nodes). TOMM20 and MCT1 were highly expressed in neoplastic lymphocytes, indicating an OXPHOS phenotype, whereas non-neoplastic lymphocytes in the control samples did not express these markers. Stromal cells in DLBCL samples strongly expressed MCT4, displaying a glycolytic phenotype, a feature not seen in stromal elements of non-neoplastic lymphatic tissue. Furthermore, the differential expression of lactate exporters (MCT4) on tumor-associated stroma and lactate importers (MCT1) on neoplastic lymphocytes support the hypothesis that neoplastic cells are metabolically linked to the stroma likely via mutually beneficial reprogramming. MCT4 is a marker of tumor-associated stroma in neoplastic tissue. Our findings suggest that disruption of neoplastic-stromal cell metabolic heterogeneity including MCT1 and MCT4 blockade should be studied to determine if it could represent a novel treatment target in DLBCL. (C) 2017 Elsevier Inc. All rights reserved.

引用

页码：204 / 217

页数：14

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