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Transl Oncol. 2019 Jun 14;12(9):1155-1163. doi: 10.1016/j.tranon.2019.04.016. [Epub ahead of print]

High Glucose Promotes Human Glioblastoma Cell Growth by Increasing the Expression and Function of Chemoattractant and Growth Factor Receptors.

Author information

1
Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA.
2
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA.
3
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA; Department of Breast Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
4
Basic Research Program, Leidos Biomedical Research, Inc., Frederick, MD 21702, USA.
5
Maternal and Child Health Care Hospital of Shandong Province, Jinan, Shandong 250002, China; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA.
6
Department of Immunology, School of Basic Medical Sciences, and Key Laboratory of Medical Immunology of Ministry of Health, Peking University Health Science Center, Beijing 100191, China; Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA.
7
Department of Pulmonary and Critical Care Medicine, Shanghai Institute of Respiratory Disease, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address: doctor_zhou_99@163.com.
8
Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute at Frederick, MD 21702, USA. Electronic address: wangji@mail.nih.gov.

Abstract

Diabetes mellitus, characterized by hyperglycemia, is considered as a risk factor of cancers including malignant gliomas. However, the direct effect of high glucose on cancer cell behavior is not clear. We therefore investigated the effect of hyperglycemia on the growth of human glioblastoma (GBM) cells. Our results revealed that high glucose (HG) promoted the proliferation and inhibited the apoptosis of a human GBM cell line U87. Mechanistically, HG upregulated the expression and function of a G-protein coupled chemoattractant receptor (GPCR) formyl peptide receptor 1 (FPR1) and epidermal growth factor receptor (EGFR) on GBM cells, which upon activation by their agonists, promoted cell migration and proliferation. In addition, the invasiveness and the production of VEGF by U87 cells were enhanced under HG conditions, the effects of which were mediated by FPR1 and EGFR agonists. The tumor promoting activity of HG was further substantiated by increased tumorigenicity and growth of xenograft tumors formed by GBM cells in nude mice with induced diabetes mellitus. Thus, our study demonstrates the capacity of HG to promote GBM progression via enhancement of the function of chemoattractant and growth factor receptors.

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