Reverse Warburg Effect in a Patient With Aggressive B-Cell Lymphoma: Is Lactic Acidosis a Paraneoplastic Syndrome?

Martinez‐Outschoorn, Ubaldo; Whitaker‐Menezes, Diana; Valsecchi, Matías E.; Cantarin, Maria P. Martinez; Dulau‐Florea, Alina; Gong, Jerald Z.; Howell, Anthony; Flomenberg, Neal; Pestell, Richard G.; Wagner, John E.; Yi, Cecilia Arana; Sharma, Manish; Sotgia, Federica; Lisanti, Michael P.

doi:10.1053/j.seminoncol.2013.04.016

Cited by 39 publications

(41 citation statements)

References 101 publications

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“…The monocarboxylate transporters are membrane proteins involved in facilitated transport (proton-linked passive symport) of lactate and other high-energy metabolites such as pyruvate and ketones 3132 . This transport can be bidirectional, driven by concentration gradients, they are differentially expressed in tissues, and are regulated by oxygen and nutrient availability 33 .…”

Section: Introductionmentioning

confidence: 99%

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

Gooptu

Whitaker‐Menezes

Sprandio

et al. 2017

Seminars in Oncology

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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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Section: Introductionmentioning

confidence: 99%

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

Gooptu

Whitaker‐Menezes

Sprandio

et al. 2017

Seminars in Oncology

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Section: Discussionmentioning

confidence: 99%

“…Patients with lymphoma induced lactic acidosis are often critically ill and it is difficult to conclude whether the etiology of lactic acidosis is completely a result of malignancy and not other potential cause such as sepsis [10, 11]. Lactic acidosis secondary to lymphoma is considered a paraneoplastic syndrome [10]. Proposed mechanisms of pathogenesis include increased glycolytic activity causing an increase in lactic acid generation, overexpression of the glycolytic enzyme hexokinase II or increased IGF-binding protein (IGFBP) activity [9, 11].…”

Section: Discussionmentioning

confidence: 99%

Complete Heart Block and Persistent Lactic Acidosis as an Initial Presentation of Non-Hodgkin Lymphoma in a Critically Ill Newly Diagnosed AIDS Patient

Ijaz

Tariq

Niazi

et al. 2014

Case Reports in Critical Care

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A 66-year-old male with newly diagnosed untreated acquired immunodeficiency syndrome (AIDS) presented with chronic nonspecific complaints of weakness, fatigue, myalgia, and weight loss. His initial EKG showed complete heart block necessitating temporary pacemaker placement. He had no previous history of cardiac disease. He was also found to have a persistent lactic acidosis and imaging studies showed abdominal lymphadenopathy. The patient underwent biopsy of these lymph nodes and was found to have diffuse large B-cell lymphoma. The hospital course was complicated by respiratory failure requiring mechanical ventilator support and cardiac arrest. Patient remained critically ill; he was not a candidate for chemotherapy and, after a month of hospitalization, he died. Lactic acidosis and heart block as an initial presentation of non-Hodgkin lymphoma in an AIDS patient are an unusual and unique presentation.

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“…In cancer models, studies by Lisanti M.P. and collaborators described the importance of cancer-associated fibroblasts in fuelling and sustaining tumour growth and the importance of MCTs in this context [71,72], namely in breast cancer [73] and B-cell lymphoma [74]. In prostate cancer, Fiaschi T. et al described that prostate cancer cells gradually became independent of glucose consumption, accompanied by a dependence on lactate uptake, to drive anabolic pathways for cell growth.…”

Section: Diagnostic and Prognostic Value Of Mcts In Prostate Cancermentioning

confidence: 99%

Lactate Transporters in the Context of Prostate Cancer Metabolism: What Do We Know?

Pértega‐Gomes

Baltazar

2014

IJMS

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Metabolic changes during malignant transformation have been noted for many years in tumours. Otto Warburg first reported that cancer cells preferentially rely on glycolysis for energy production, even in the presence of oxygen, leading to the production of high levels of lactate. The crucial role of lactate efflux and exchange within the tumour microenvironment drew attention to monocarboxylate transporters (MCTs). MCTs have been recognized as promising targets in cancer therapy, and their expression was described in a large variety of tumours; however, studies showing how these isoforms contribute to the acquisition of the malignant phenotype are scarce and still unclear regarding prostate cancer. In this review, we focus on the role for MCTs in cell metabolism, supporting the development and progression of prostate cancer, and discuss the exploitation of the metabolic nature of prostate cancer for therapeutic and diagnostic purposes.

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Reverse Warburg Effect in a Patient With Aggressive B-Cell Lymphoma: Is Lactic Acidosis a Paraneoplastic Syndrome?

Cited by 39 publications

References 101 publications

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

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

Complete Heart Block and Persistent Lactic Acidosis as an Initial Presentation of Non-Hodgkin Lymphoma in a Critically Ill Newly Diagnosed AIDS Patient

Lactate Transporters in the Context of Prostate Cancer Metabolism: What Do We Know?

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