ArticleExperimental cell research2017
Tumor stroma interaction is mediated by monocarboxylate metabolism.
Article in Experimental cell research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 42 citations in OpenAlex.
- Targeting the tumor microenvironment: a new strategy for natural products in breast cancer therapy.Natural products and bioprospecting · 2026Review
- Deuterium metabolic imaging phenotypes mouse glioblastoma heterogeneity through glucose turnover kinetics.eLife · 2025Article
- Merging metabolic modeling and imaging for screening therapeutic targets in colorectal cancer.NPJ systems biology and applications · 2025Article
- Envisioning Glucose Transporters (GLUTs and SGLTs) as Novel Intervention against Cancer: Drug Discovery Perspective and Targeting Approach.Current drug targets · 2025Review
- Merging Metabolic Modeling and Imaging for Screening Therapeutic Targets in Colorectal Cancer.bioRxiv : the preprint server for biology · 2024Article
- Single-cell decoding of drug induced transcriptomic reprogramming in triple negative breast cancers.Genome biology · 2024Article
- Article
- Review
- Tumor-Derived Lactate Creates a Favorable Niche for TumorFrontiers in cell and developmental biology · 2022Review
- Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma.Cancer & metabolism · 2021Article
- Natural Compounds as Metabolic Modulators of the Tumor Microenvironment.Molecules (Basel, Switzerland) · 2021Review
- Metabolic Interactions Between Tumor and Stromal Cells in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021Article
- Mitochondria at Center of Exchanges between Cancer Cells and Cancer-Associated Fibroblasts during Tumor Progression.Cancers · 2020Review
- Revisiting lactate dynamics in cancer-a metabolic expertise or an alternative attempt to survive?Journal of molecular medicine (Berlin, Germany) · 2020Review
- A Perspective on Expanding Our Understanding of Cancer Treatments by Integrating Approaches from the Biological and Physical Sciences.SLAS discovery : advancing life sciences R & D · 2020Article
- Distinguishing metastatic triple-negative breast cancer from nonmetastatic breast cancer using second harmonic generation imaging and resonance Raman spectroscopy.Journal of biophotonics · 2020Article
- Role of Proton-Coupled Monocarboxylate Transporters in Cancer: From Metabolic Crosstalk to Therapeutic Potential.Frontiers in cell and developmental biology · 2020Review
- Metabolic Reprogramming in Triple-Negative Breast Cancer.Frontiers in oncology · 2020Review
- Lactate Dehydrogenases as Metabolic Links between Tumor and Stroma in the Tumor Microenvironment.Cancers · 2019Review
- Mutual concessions and compromises between stromal cells and cancer cells: driving tumor development and drug resistance.Cellular oncology (Dordrecht, Netherlands) · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human breast tumors contain significant amounts of stromal cells. There exists strong evidence that these stromal cells support cancer development and progression by altering various pathways (e.g. downregulation of tumor suppressor genes or autocrine signaling loops). Here, we suggest that stromal carcinoma-associated fibroblasts (CAFs), shown to be generated from bone marrow-derived mesenchymal stem cells, may (i) recycle tumor-derived lactate for their own energetic requirements, thereby sparing glucose for neighboring glycolytic tumor cells, and (ii) subsequently secrete surplus energetically and biosynthetically valuable metabolites of lactate oxidation, such as pyruvate, to support tumor growth. Lactate, taken up by stromal CAFs, is converted to pyruvate, which is then utilized by CAFs for energy needs as well as excreted and shared with tumor cells. We have interrogated lactate oxidation in CAFs to determine what metabolites may be secreted, and how they may affect the metabolism and growth of MDA-MB-231 breast cancer cells. We found that CAFs secrete pyruvate as a metabolite of lactate oxidation. Further, we show that pyruvate is converted to lactate to promote glycolysis in MDA-MB-231 cells and helps to control elevated ROS levels in these tumor cells. Finally, we found that inhibiting or interfering with ROS management, using the naturally occurring flavonoid phloretin (found in apple tree leaves), adds to the cytotoxicity of the conventional chemotherapeutic agent doxorubicin. Our work demonstrates that a lactate-pyruvate, reciprocally-supportive metabolic relationship may be operative within the tumor microenvironment (TME) to support tumor growth, and may be a useful drug target.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.