ArticleOncotarget2015
Bladder cancer cells re-educate TAMs through lactate shuttling in the microfluidic cancer microenvironment.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review).Experimental and therapeutic medicine · 2026Review
- Lactate metabolic reprogramming and lactylation modification: molecular mechanisms reshaping the tumor immunosuppressive microenvironment.Cell & bioscience · 2026Review
- Lactic Acid in Tumour Biology.Metabolites · 2026Review
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- BCG therapy in bladder cancer and its tumor microenvironment interactions.Clinical microbiology reviews · 2025Review
- Tumor Microenvironment Lactate: Is It a Cancer Progression Marker, Immunosuppressant, and Therapeutic Target?Molecules (Basel, Switzerland) · 2025Review
- SLC16A3 is a Prognostic Marker and Affects Immune Regulation in Bladder Cancer.Combinatorial chemistry & high throughput screening · 2025Article
- Targeting the hypoxia signaling pathway with nanomedicine to reverse immunotherapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Practical Characterization Strategies for Comparison, Qualification, and Selection of Cell Viability Detection Methods for Cellular Therapeutic Product Development and Manufacturing.Journal of fluorescence · 2024Article
- Lactate activates CCL18 expression via H3K18 lactylation in macrophages to promote tumorigenesis of ovarian cancer.Acta biochimica et biophysica Sinica · 2024Article
- Article
- Advances in tumor microenvironment and underlying molecular mechanisms of bladder cancer: a systematic review.Discover oncology · 2024Review
- Tetralol derivative NNC-55-0396 targets hypoxic cells in the glioblastoma microenvironment: an organ-on-chip approach.Cell death & disease · 2024Article
- Tumor-associated macrophages in bladder cancer: roles and targeted therapeutic strategies.Frontiers in immunology · 2024Review
- Advances in macrophage and T cell metabolic reprogramming and immunotherapy in the tumor microenvironment.PeerJ · 2024Article
- Breaking the mold: 3D cell cultures reshaping the future of cancer research.Frontiers in cell and developmental biology · 2024Review
- A feed-forward loop based on aerobic glycolysis and TGF-β between tumor-associated macrophages and bladder cancer cells promoted malignant progression and immune escape.Journal of cancer research and clinical oncology · 2023Article
- Review
- Tumour microenvironment as a predictive factor for immunotherapy in non-muscle-invasive bladder cancer.Cancer immunology, immunotherapy : CII · 2023Review
- Efficacy of recombinant Bacillus Calmette-Guérin containing dltA inInvestigative and clinical urology · 2023Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn the present study, we aimed to investigate the influence of lactate shuttling on the functional polarization and spatial distribution of transitional cell carcinoma of the bladder (TCCB) cells and macrophages.
methodsWe designed a microfluidic coculture chip for real-time integrative assays. The effect of lactate shuttling on the re-education of macrophages by TCCB cells was explored by measuring the levels of NO using a total NO assay kit and by evaluating the protein expression of iNOS, p-NFkB-p65, Arg-1 and HIF-1α via cell immunofluorescence and western blotting. Additionally, we examined TCCB cell viability using acridine orange/ethidium bromide (AO/EB) and MitoTracker staining. Moreover, the concentration distributions of lactate and large signaling proteins in the culture chambers were measured using 4',6-diamidino-2-phenylindole (DAPI) and fluorescein isothiocyanate-dextran (FITC-dextran). Furthermore, the recruitment of macrophages and the influence of macrophages on BC metastasis were observed via light microscopy.
resultsWe confirmed that TCCB cells reprogrammed macrophages into an M2 phenotype. Moreover, lactate inhibited M1 polarization and induced M2 polarization of macrophages, but blockade of cancer cell-macrophage lactate flux significantly inhibited the re-education of macrophages by TCCB cells. In addition, lactate diffused faster and deeper than large signaling proteins in the microfluidic tumor microenvironment. Furthermore, lactate alone induced the migration of macrophages, and M1, but not M2, macrophages reduced the motility of TCCB cells.
conclusionsTCCB cells reprogrammed macrophages into an M2 phenotype in a manner that depended on cancer cell-TAM lactate flux. Furthermore, the lactate shuttle may be a determinant of the density of TAMs in tumor tissue.
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