Mitochondrial and glycolytic metabolic compartmentalization in diffuse large B-cell lymphoma.
Mitochondrial and glycolytic metabolic compartmentalization in diffuse large B-cell lymphoma.
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DOI：
10.1053/j.seminoncol.2017.10.002
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发表时间：
2017-06
影响因子：
4
通讯作者：
Martinez-Outschoorn U
中科院分区：
文献类型：
--
作者：
Gooptu M;Whitaker-Menezes D;Sprandio J;Domingo-Vidal M;Lin Z;Uppal G;Gong J;Fratamico R;Leiby B;Dulau-Florea A;Caro J;Martinez-Outschoorn U
肿瘤细胞和周围基质之间的代谢异质性已经在一些上皮恶性肿瘤中被描述；然而，弥漫大b细胞淋巴瘤（DLBCL）中肿瘤淋巴细胞和邻近基质的代谢表型尚不清楚。我们利用糖酵解和线粒体氧化磷酸化（OXPHOS）代谢的免疫组织化学标记物研究了人DLBCL肿瘤的代谢表型。乳酸输入基因MCT4是糖酵解的标记，而乳酸输入基因MCT1和TOMM20是OXPHOS代谢的标记。对33例DLBCL样本和18例对照样本（非肿瘤性淋巴结）的染色模式进行了评估。TOMM20和MCT1在肿瘤淋巴细胞中高表达，表明OXPHOS表型，而对照样本中的非肿瘤淋巴细胞不表达这些标记物。DLBCL样本中的基质细胞强烈表达MCT4，表现为糖酵解表型，这一特征在非肿瘤淋巴组织的基质细胞中未见。此外，肿瘤相关基质上乳酸输出蛋白（MCT4）和肿瘤淋巴细胞上乳酸输入蛋白（MCT1）的差异表达支持了肿瘤细胞可能通过互利的重编程与基质代谢相关的假设。MCT4是肿瘤组织中肿瘤相关基质的标志物。我们的研究结果表明，应该研究肿瘤基质细胞代谢异质性的破坏，包括MCT1和MCT4阻断，以确定它是否可以代表DLBCL的新治疗靶点。
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 b studied to determine if it could represent a novel treatment target in DLBCL.
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影响因子：
11.2
作者：
Barsoum, Ivraym B.;Smallwood, Chelsea A.;Graham, Charles H.
通讯作者：
Graham, Charles H.
DOI：
10.4161/cc.24092
发表时间：
2013-05-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Curry JM;Tuluc M;Whitaker-Menezes D;Ames JA;Anantharaman A;Butera A;Leiby B;Cognetti DM;Sotgia F;Lisanti MP;Martinez-Outschoorn UE
通讯作者：
Martinez-Outschoorn UE
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM
影响因子：
11.2
作者：
Doherty JR;Yang C;Scott KE;Cameron MD;Fallahi M;Li W;Hall MA;Amelio AL;Mishra JK;Li F;Tortosa M;Genau HM;Rounbehler RJ;Lu Y;Dang CV;Kumar KG;Butler AA;Bannister TD;Hooper AT;Unsal-Kacmaz K;Roush WR;Cleveland JL
通讯作者：
Cleveland JL
影响因子：
4.8
作者：
Ko, Ying-Hui;Domingo-Vidal, Marina;Martinez-Outschoorn, Ubaldo
通讯作者：
Martinez-Outschoorn, Ubaldo