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A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
Published on: February 28, 2020
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Tumor stroma interaction is mediated by monocarboxylate metabolism
Brijesh B Patel1, Ellen Ackerstaff2, Inna S Serganova3
1Department of Pharmacology and Graduate School of Biomedical Sciences, Rutgers Biomedical Health Sciences, Rutgers, The State University of New Jersey, 675 Hoes Lane West, Piscataway, NJ 08854, United States.
Experimental Cell Research
|January 31, 2017
Summary
Stromal fibroblasts recycle tumor lactate, converting it to pyruvate. This metabolic exchange fuels tumor growth and offers a potential drug target for breast cancer therapy.
Area of Science:
- Oncology
- Cancer Metabolism
- Tumor Microenvironment
Background:
- Stromal cells in human breast tumors significantly influence cancer progression.
- Carcinoma-associated fibroblasts (CAFs), derived from mesenchymal stem cells, play a key role in tumor support.
- CAFs may metabolize tumor-derived lactate to influence cancer cell metabolism.
Purpose of the Study:
- To investigate the metabolic relationship between CAFs and breast cancer cells.
- To determine if CAFs recycle lactate and secrete metabolites that support tumor growth.
- To explore targeting this metabolic interaction for therapeutic benefit.
Main Methods:
- Analysis of lactate oxidation in CAFs.
- Metabolite profiling of CAF secretions.
- Assessment of pyruvate's effect on MDA-MB-231 breast cancer cell metabolism and growth.
- Evaluation of phloretin and doxorubicin combination therapy.
Main Results:
- CAFs secrete pyruvate as a lactate oxidation metabolite.
- Pyruvate supports glycolysis and reactive oxygen species (ROS) management in MDA-MB-231 cells.
- Inhibiting ROS with phloretin enhances doxorubicin's cytotoxicity.
Conclusions:
- A reciprocal lactate-pyruvate metabolic loop exists in the tumor microenvironment, supporting tumor growth.
- This metabolic interplay represents a potential therapeutic target for breast cancer.
- Targeting ROS management alongside chemotherapy shows promise.
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