TY - JOUR
T1 - Hyaluronic Acid Influences Amino Acid Metabolism via Differential L-Type Amino Acid Transporter 1 Expression in the U87-Malignant Glioma Cell Line
AU - Bale, Ashwin A.
AU - Thammineni, Swaroop
AU - Bhargava, Rohit
AU - Harley, Brendan
N1 - The authors would like to acknowledge the following institutes for access to their facilities and services: the Roy J. Carver Biotechnology Center at UIUC (assisted by Dr. Michael La Frano and Dr. Alexander Ulanov), the School of Chemical Sciences Microanalysis Laboratory, the Tumor Engineering and Phenotyping Core at the Cancer Center at Illinois (assisted by Dr. Hui Xu and Huimin Zhang), and Materials Research Laboratory (assisted by Dr. Remy Roddel). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award number R01 CA256481 (BACH) and R01 CA260830 (RB). The interpretations and conclusions presented are those of the authors and are not necessarily endorsed by the National Institutes of Health. The authors also acknowledge additional funding provided by the Cancer Center at Illinois at the University of Illinois at Urbana\u2010Champaign.
PY - 2024/9/2
Y1 - 2024/9/2
N2 - The glioblastoma (GBM) tumor microenvironment is heterogeneous, complex, and being increasingly understood as a significant contributor to tumor progression. In brain tumors, the extracellular matrix contains a large concentration of hyaluronic acid (HA) that makes it important to study its role in cancer progression. In particular, abnormal accumulation of HA is observed in gliomas and is often associated with poor prognosis. In addition, HA is a polymer and its molecular weight (MW) distribution may influence tumor cell activity. Herein, the influence of the MW of HA on tumor cell metabolism is evaluated. A 2D cell culture approach is used to expose the U87-MG (medium glucose [MG]) cell line to different HA MWs (10, 60, and 500 kDa) and glucose concentrations (0, 5.5, and 25 mm). Notably, it is found that HA influences GBM amino acid metabolism via reduction in LAT1 transporter protein expression. Also an influence on mitochondrial respiration levels and a difference in the accumulation of some key products of cell metabolic activity (lactic acid, glutamic acid, and succinic acid) are reported. Overall, in these results, it is indicated that HA MW can influence GBM metabolic state, with implications for cell invasion and tumor progression.
AB - The glioblastoma (GBM) tumor microenvironment is heterogeneous, complex, and being increasingly understood as a significant contributor to tumor progression. In brain tumors, the extracellular matrix contains a large concentration of hyaluronic acid (HA) that makes it important to study its role in cancer progression. In particular, abnormal accumulation of HA is observed in gliomas and is often associated with poor prognosis. In addition, HA is a polymer and its molecular weight (MW) distribution may influence tumor cell activity. Herein, the influence of the MW of HA on tumor cell metabolism is evaluated. A 2D cell culture approach is used to expose the U87-MG (medium glucose [MG]) cell line to different HA MWs (10, 60, and 500 kDa) and glucose concentrations (0, 5.5, and 25 mm). Notably, it is found that HA influences GBM amino acid metabolism via reduction in LAT1 transporter protein expression. Also an influence on mitochondrial respiration levels and a difference in the accumulation of some key products of cell metabolic activity (lactic acid, glutamic acid, and succinic acid) are reported. Overall, in these results, it is indicated that HA MW can influence GBM metabolic state, with implications for cell invasion and tumor progression.
KW - amino acids
KW - glioblastomas
KW - glucoses
KW - hyaluronic acids
KW - metabolisms
KW - molecular weights
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U2 - 10.1002/anbr.202400107
DO - 10.1002/anbr.202400107
M3 - Article
AN - SCOPUS:85202831839
SN - 2699-9307
VL - 4
JO - Advanced NanoBiomed Research
JF - Advanced NanoBiomed Research
IS - 12
M1 - 2400107
ER -