ArticleLaboratory investigation; a journal of technical methods and pathology2017
Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts.
Article in Laboratory investigation; a journal of technical methods and pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
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- Sirtuin1 (sirt1) regulates the glycolysis pathway and decreases cisplatin chemotherapeutic sensitivity to esophageal squamous cell carcinoma.Cancer biology & therapy · 2024Article
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- Co-Culture Device for in vitro High Throughput Analysis of Cancer-Associated Fibroblast and Cancer Cell Interactions.Oncology · 2024Article
- Bridging the gap: advancing cancer cell culture to reveal key metabolic targets.Frontiers in oncology · 2024Review
- Shedding light on macrophage immunotherapy in lung cancer.Journal of cancer research and clinical oncology · 2023Review
- Applications and Advances of Multicellular Tumor Spheroids: Challenges in Their Development and Analysis.International journal of molecular sciences · 2023Review
- A Synergistic pH-Responsive Serum Albumin-Based Drug Delivery System Loaded with Doxorubicin and Pentacyclic Triterpene Betulinic Acid for Potential Treatment of NSCLC.Biotech (Basel (Switzerland)) · 2023Article
- Appropriate cold stimulation changes energy distribution to improve stress resistance in broilers.Journal of animal science · 2023Article
- Effect of Sublethal Copper Overload on CholesterolACS omega · 2022Article
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- Mitochondria dysfunction in circulating tumor cells.Frontiers in oncology · 2022Review
- Identification of Hub Genes in Idiopathic Pulmonary Fibrosis and NSCLC Progression:Evidence From Bioinformatics Analysis.Frontiers in genetics · 2022Article
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- Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.Frontiers in cellular and infection microbiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1. In contrast, cancer cells increase the expression of glucose transporters (GLUT1), LDH5, PDH kinase and the levels of phosphorylated/inactivated pPDH. H1299 cells growing in the same culture medium with fibroblasts exhibit a 'metastasis-like' phenomenon by forming nests within the fibroblast area. LDH5 and pPDH were drastically upregulated in these nests. The growth rate of both MRC5 and cancer cells increased in co-cultures. Suppression of LDHA or PDK1 in cancer cells abrogates the stimulatory signal from cancer cells to fibroblasts. Incubation of MRC5 fibroblasts with lactate resulted in an increase of LDHB and of PDH expression. Silencing of PDH gene in fibroblasts, or silencing of PDK1 or LDHA gene in tumor cells, impedes cancer cell's migration ability. Overall, a metabolic cooperation between lung cancer cells and fibroblasts has been confirmed in the context of direct Warburg effect, thus the fibroblasts reinforce aerobic metabolism to support the intensified anaerobic glycolytic pathways exploited by cancer cells.
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