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Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay
Tania Fiaschi1, Alberto Marini, Elisa Giannoni
1Department of Biochemical Sciences, Tuscany Tumor Institute and Center for Research, Transfer and High Education DenoTHE, University of Florence, Florence, Italy.
Cancer Research
|August 2, 2012
Summary
Cancer cells reprogram stromal fibroblasts to produce lactate (Warburg metabolism), which prostate cancer cells then use for growth. This metabolic symbiosis aids tumor progression and survival in low-glucose environments.
Area of Science:
- Oncology
- Cancer Metabolism
- Cell Biology
Background:
- Cancer-associated fibroblasts (CAFs) promote tumor progression, epithelial-mesenchymal transition (EMT), and metastasis.
- The interplay between CAFs and cancer cells involves complex signaling beyond EMT, including metabolic reprogramming.
Purpose of the Study:
- To investigate the mutual metabolic reprogramming between CAFs and prostate cancer cells.
- To elucidate the role of metabolic symbiosis in prostate cancer progression.
Main Methods:
- Gene expression analysis of CAFs and prostate fibroblasts.
- Investigating metabolic changes in cancer cells and fibroblasts upon intercellular contact.
- Pharmacologic inhibition of lactate transporters.
Main Results:
- CAFs exhibit Warburg metabolism and mitochondrial oxidative stress, driven by contact with prostate cancer cells.
- Prostate cancer cells switch to aerobic metabolism, utilizing lactate supplied by CAFs via MCT1.
- Hypoxia-inducible factor 1 (HIF1) controls metabolic reprogramming in both cell types.
- Inhibition of MCT1-mediated lactate uptake significantly impairs cancer cell survival and tumor growth.
Conclusions:
- Prostate cancer cells induce a Warburg phenotype in CAFs to generate lactate.
- Cancer cells exploit CAF-derived lactate for growth and survival, especially in low-glucose conditions.
- This metabolic symbiosis represents a novel mechanism of tumor adaptation and progression.
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